Genomic Imprinting Syndromes and Cancer

  • Ken Higashimoto
  • Keiichiro Joh
  • Hidenobu Soejima
Part of the Cancer Drug Discovery and Development book series (CDD&D)


Genomic imprinting is an epigenetic phenomenon that leads to parent-specific differential expression of a subset of mammalian genes. Some imprinted genes are expressed from the maternal allele and repressed on the paternal allele, whereas others are expressed from the paternal and not the maternal allele. Because most imprinted genes play important roles in growth and development, and metabolism, the aberrant expression of imprinted genes due to epigenetic or genetic alterations often causes human disorders. These include genomic imprinting syndromes and tumors. Since loss of imprinting (LOI) of IGF2 (which means biallelic expression of IGF2) was first reported in Wilms tumor in 1993, aberrant methylation of differentially methylated regions (DMRs), which regulate expression of imprinted genes and/or aberrant expression of imprinted genes, have been reported in various tumors. In this section, general imprinting mechanisms, representative clinical features and causative molecular alterations of eight imprinting syndromes are described. In addition, representative molecular alterations of imprinted DMRs or imprinted genes associated with tumors are also described.


Genomic imprinting Imprinting syndromes Imprinted genes Differentially methylated regions (DMRs) Imprinting control regions (ICRs) 


  1. 1.
    Abdollahi A (2007) LOT1 (ZAC1/PLAGL1) and its family members: mechanisms and functions. J Cell Physiol 210(1):16–25. doi: 10.1002/jcp.20835 PubMedCrossRefGoogle Scholar
  2. 2.
    Abramowitz LK, Bartolomei MS (2012) Genomic imprinting: recognition and marking of imprinted loci. Curr Opin Genet Dev 22(2):72–78. doi: 10.1016/j.gde.2011.12.001 PubMedCrossRefGoogle Scholar
  3. 3.
    Algar EM, Muscat A, Dagar V, Rickert C, Chow CW, Biegel JA, Ekert PG, Saffery R, Craig J, Johnstone RW, Ashley DM (2009) Imprinted CDKN1C is a tumor suppressor in rhabdoid tumor and activated by restoration of SMARCB1 and histone deacetylase inhibitors. PLoS One 4(2):e4482. doi: 10.1371/journal.pone.0004482 PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Amatruda JF, Ross JA, Christensen B, Fustino NJ, Chen KS, Hooten AJ, Nelson H, Kuriger JK, Rakheja D, Frazier AL, Poynter JN (2013) DNA methylation analysis reveals distinct methylation signatures in pediatric germ cell tumors. BMC Cancer 13:313. doi: 10.1186/1471-2407-13-313 PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    An F, Yamanaka S, Allen S, Roberts LR, Gores GJ, Pawlik TM, Xie Q, Ishida M, Mezey E, Ferguson-Smith AC, Mori Y, Selaru FM (2012) Silencing of miR-370 in human cholangiocarcinoma by allelic loss and interleukin-6 induced maternal to paternal epigenotype switch. PLoS One 7(10):e45606. doi: 10.1371/journal.pone.0045606 PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Anwar SL, Krech T, Hasemeier B, Schipper E, Schweitzer N, Vogel A, Kreipe H, Lehmann U (2012) Loss of imprinting and allelic switching at the DLK1-MEG3 locus in human hepatocellular carcinoma. PLoS One 7(11):e49462. doi: 10.1371/journal.pone.0049462 PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Anwar SL, Krech T, Hasemeier B, Schipper E, Schweitzer N, Vogel A, Kreipe H, Lehmann U (2014) Deregulation of RB1 expression by loss of imprinting in human hepatocellular carcinoma. J Pathol 233(4):392–401. doi: 10.1002/path.4376 PubMedCrossRefGoogle Scholar
  8. 8.
    Anwar SL, Krech T, Hasemeier B, Schipper E, Schweitzer N, Vogel A, Kreipe H, Lehmann U (2015) Loss of DNA methylation at imprinted loci is a frequent event in hepatocellular carcinoma and identifies patients with shortened survival. Clin Epigenetics 7:110. doi: 10.1186/s13148-015-0145-6 PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Arima T, Matsuda T, Takagi N, Wake N (1997) Association of IGF2 and H19 imprinting with choriocarcinoma development. Cancer Genet Cytogenet 93(1):39–47PubMedCrossRefGoogle Scholar
  10. 10.
    Astuti D, Latif F, Wagner K, Gentle D, Cooper WN, Catchpoole D, Grundy R, Ferguson-Smith AC, Maher ER (2005) Epigenetic alteration at the DLK1-GTL2 imprinted domain in human neoplasia: analysis of neuroblastoma, phaeochromocytoma and Wilms' tumour. Br J Cancer 92(8):1574–1580. doi: 10.1038/sj.bjc.6602478 PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Baba Y, Nosho K, Shima K, Huttenhower C, Tanaka N, Hazra A, Giovannucci EL, Fuchs CS, Ogino S (2010) Hypomethylation of the IGF2 DMR in colorectal tumors, detected by bisulfite pyrosequencing, is associated with poor prognosis. Gastroenterology 139(6):1855–1864. doi: 10.1053/j.gastro.2010.07.050 PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Barrow TM, Barault L, Ellsworth RE, Harris HR, Binder AM, Valente AL, Shriver CD, Michels KB (2015) Aberrant methylation of imprinted genes is associated with negative hormone receptor status in invasive breast cancer. Int J Cancer 137(3):537–547. doi: 10.1002/ijc.29419 PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Bastepe M (2007) The GNAS Locus: Quintessential Complex Gene Encoding Gsalpha, XLalphas, and other Imprinted Transcripts. Curr Genomics 8(6):398–414. doi: 10.2174/138920207783406488 PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Bell AC, Felsenfeld G (2000) Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene. Nature 405(6785):482–485. doi: 10.1038/35013100 PubMedCrossRefGoogle Scholar
  15. 15.
    Benetatos L, Hatzimichael E, Dasoula A, Dranitsaris G, Tsiara S, Syrrou M, Georgiou I, Bourantas KL (2010) CpG methylation analysis of the MEG3 and SNRPN imprinted genes in acute myeloid leukemia and myelodysplastic syndromes. Leuk Res 34(2):148–153. doi: 10.1016/j.leukres.2009.06.019 PubMedCrossRefGoogle Scholar
  16. 16.
    Bjornsson HT, Brown LJ, Fallin MD, Rongione MA, Bibikova M, Wickham E, Fan JB, Feinberg AP (2007) Epigenetic specificity of loss of imprinting of the IGF2 gene in Wilms tumors. J Natl Cancer Inst 99(16):1270–1273. doi: 10.1093/jnci/djm069 PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Borriello A, Caldarelli I, Bencivenga D, Criscuolo M, Cucciolla V, Tramontano A, Oliva A, Perrotta S, Della Ragione F (2011) p57(Kip2) and cancer: time for a critical appraisal. Mol Cancer Res 9(10):1269–1284. doi: 10.1158/1541-7786.MCR-11-0220 PubMedCrossRefGoogle Scholar
  18. 18.
    Bourc'his D, Xu GL, Lin CS, Bollman B, Bestor TH (2001) Dnmt3L and the establishment of maternal genomic imprints. Science 294(5551):2536–2539. doi: 10.1126/science.1065848 PubMedCrossRefGoogle Scholar
  19. 19.
    Boyce AM, Collins MT (1993) Fibrous dysplasia/McCune-Albright syndrome. In: Pagon RA, Adam MP, Ardinger HH et al (eds) GeneReviews®. University of Washington, Seattle, WAGoogle Scholar
  20. 20.
    Braconi C, Kogure T, Valeri N, Huang N, Nuovo G, Costinean S, Negrini M, Miotto E, Croce CM, Patel T (2011) microRNA-29 can regulate expression of the long non-coding RNA gene MEG3 in hepatocellular cancer. Oncogene 30(47):4750–4756. doi: 10.1038/onc.2011.193 PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Brouwer-Visser J, Huang GS (2015) IGF2 signaling and regulation in cancer. Cytokine Growth Factor Rev 26(3):371–377. doi: 10.1016/j.cytogfr.2015.01.002 PubMedCrossRefGoogle Scholar
  22. 22.
    Brouwer-Visser J, Lee J, McCullagh K, Cossio MJ, Wang Y, Huang GS (2014) Insulin-like growth factor 2 silencing restores taxol sensitivity in drug resistant ovarian cancer. PLoS One 9(6):e100165. doi: 10.1371/journal.pone.0100165 PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Buiting K (2010) Prader-Willi syndrome and Angelman syndrome. Am J Med Genet C Semin Med Genet 154C(3):365–376. doi: 10.1002/ajmg.c.30273 PubMedCrossRefGoogle Scholar
  24. 24.
    Byun HM, Wong HL, Birnstein EA, Wolff EM, Liang G, Yang AS (2007) Examination of IGF2 and H19 loss of imprinting in bladder cancer. Cancer Res 67(22):10753–10758. doi: 10.1158/0008-5472.CAN-07-0329 PubMedCrossRefGoogle Scholar
  25. 25.
    Charlton J, Williams RD, Sebire NJ, Popov S, Vujanic G, Chagtai T, Alcaide-German M, Morris T, Butcher LM, Guilhamon P, Beck S, Pritchard-Jones K (2015) Comparative methylome analysis identifies new tumour subtypes and biomarkers for transformation of nephrogenic rests into Wilms tumour. Genome Med 7(1):11. doi: 10.1186/s13073-015-0136-4 PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Chen J, Wang M, Guo M, Xie Y, Cong YS (2013) miR-127 regulates cell proliferation and senescence by targeting BCL6. PLoS One 8(11):e80266. doi: 10.1371/journal.pone.0080266 PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Chen XP, Chen YG, Lan JY, Shen ZJ (2014) MicroRNA-370 suppresses proliferation and promotes endometrioid ovarian cancer chemosensitivity to cDDP by negatively regulating ENG. Cancer Lett 353(2):201–210. doi: 10.1016/j.canlet.2014.07.026 PubMedCrossRefGoogle Scholar
  28. 28.
    Cheng YW, Idrees K, Shattock R, Khan SA, Zeng Z, Brennan CW, Paty P, Barany F (2010) Loss of imprinting and marked gene elevation are 2 forms of aberrant IGF2 expression in colorectal cancer. Int J Cancer 127(3):568–577. doi: 10.1002/ijc.25086 PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Chotalia M, Smallwood SA, Ruf N, Dawson C, Lucifero D, Frontera M, James K, Dean W, Kelsey G (2009) Transcription is required for establishment of germline methylation marks at imprinted genes. Genes Dev 23(1):105–117. doi: 10.1101/gad.495809 PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Ciccone DN, Su H, Hevi S, Gay F, Lei H, Bajko J, Xu G, Li E, Chen T (2009) KDM1B is a histone H3K4 demethylase required to establish maternal genomic imprints. Nature 461(7262):415–418. doi: 10.1038/nature08315 PubMedCrossRefGoogle Scholar
  31. 31.
    Cui H (2007) Loss of imprinting of IGF2 as an epigenetic marker for the risk of human cancer. Dis Markers 23(1-2):105–112PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Cui H, Cruz-Correa M, Giardiello FM, Hutcheon DF, Kafonek DR, Brandenburg S, Wu Y, He X, Powe NR, Feinberg AP (2003) Loss of IGF2 imprinting: a potential marker of colorectal cancer risk. Science 299(5613):1753–1755. doi: 10.1126/science.1080902 PubMedCrossRefGoogle Scholar
  33. 33.
    Cui H, Horon IL, Ohlsson R, Hamilton SR, Feinberg AP (1998) Loss of imprinting in normal tissue of colorectal cancer patients with microsatellite instability. Nat Med 4(11):1276–1280. doi: 10.1038/3260 PubMedCrossRefGoogle Scholar
  34. 34.
    Cui H, Niemitz EL, Ravenel JD, Onyango P, Brandenburg SA, Lobanenkov VV, Feinberg AP (2001) Loss of imprinting of insulin-like growth factor-II in Wilms' tumor commonly involves altered methylation but not mutations of CTCF or its binding site. Cancer Res 61(13):4947–4950PubMedGoogle Scholar
  35. 35.
    Cui H, Onyango P, Brandenburg S, Wu Y, Hsieh CL, Feinberg AP (2002) Loss of imprinting in colorectal cancer linked to hypomethylation of H19 and IGF2. Cancer Res 62(22):6442–6446PubMedGoogle Scholar
  36. 36.
    da Rocha ST, Edwards CA, Ito M, Ogata T, Ferguson-Smith AC (2008) Genomic imprinting at the mammalian Dlk1-Dio3 domain. Trends Genet 24(6):306–316. doi: 10.1016/j.tig.2008.03.011 PubMedCrossRefGoogle Scholar
  37. 37.
    Dai H, Huang Y, Li Y, Meng G, Wang Y, Guo QN (2012) TSSC3 overexpression associates with growth inhibition, apoptosis induction and enhances chemotherapeutic effects in human osteosarcoma. Carcinogenesis 33(1):30–40. doi: 10.1093/carcin/bgr232 PubMedCrossRefGoogle Scholar
  38. 38.
    Dammann RH, Kirsch S, Schagdarsurengin U, Dansranjavin T, Gradhand E, Schmitt WD, Hauptmann S (2010) Frequent aberrant methylation of the imprinted IGF2/H19 locus and LINE1 hypomethylation in ovarian carcinoma. Int J Oncol 36(1):171–179PubMedGoogle Scholar
  39. 39.
    Davies HD, Leusink GL, McConnell A, Deyell M, Cassidy SB, Fick GH, Coppes MJ (2003) Myeloid leukemia in Prader-Willi syndrome. J Pediatr 142(2):174–178. doi: 10.1067/mpd.2003.81 PubMedCrossRefGoogle Scholar
  40. 40.
    De Castro Valente Esteves LI, De Karla CN, Do Carmo Javaroni A, Magrin J, Kowalski LP, Rainho CA, Rogatto SR (2006) H19-DMR allele-specific methylation analysis reveals epigenetic heterogeneity of CTCF binding site 6 but not of site 5 in head-and-neck carcinomas: a pilot case-control analysis. Int J Mol Med 17(2):397–404PubMedGoogle Scholar
  41. 41.
    de Smith AJ, Purmann C, Walters RG, Ellis RJ, Holder SE, Van Haelst MM, Brady AF, Fairbrother UL, Dattani M, Keogh JM, Henning E, Yeo GS, O'Rahilly S, Froguel P, Farooqi IS, Blakemore AI (2009) A deletion of the HBII-85 class of small nucleolar RNAs (snoRNAs) is associated with hyperphagia, obesity and hypogonadism. Hum Mol Genet 18(17):3257–3265. doi: 10.1093/hmg/ddp263 PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Dejeux E, Olaso R, Dousset B, Audebourg A, Gut IG, Terris B, Tost J (2009) Hypermethylation of the IGF2 differentially methylated region 2 is a specific event in insulinomas leading to loss-of-imprinting and overexpression. Endocr Relat Cancer 16(3):939–952. doi: 10.1677/ERC-08-0331 PubMedCrossRefGoogle Scholar
  43. 43.
    Denduluri SK, Idowu O, Wang Z, Liao Z, Yan Z, Mohammed MK, Ye J, Wei Q, Wang J, Zhao L, Luu HH (2015) Insulin-like growth factor (IGF) signaling in tumorigenesis and the development of cancer drug resistance. Genes Dis 2(1):13–25. doi: 10.1016/j.gendis.2014.10.004 PubMedCrossRefGoogle Scholar
  44. 44.
    Douc-Rasy S, Barrois M, Fogel S, Ahomadegbe JC, Stéhelin D, Coll J, Riou G (1996) High incidence of loss of heterozygosity and abnormal imprinting of H19 and IGF2 genes in invasive cervical carcinomas. Uncoupling of H19 and IGF2 expression and biallelic hypomethylation of H19. Oncogene 12(2):423–430PubMedGoogle Scholar
  45. 45.
    Dowdy SC, Gostout BS, Shridhar V, Wu X, Smith DI, Podratz KC, Jiang SW (2005) Biallelic methylation and silencing of paternally expressed gene 3 (PEG3) in gynecologic cancer cell lines. Gynecol Oncol 99(1):126–134. doi: 10.1016/j.ygyno.2005.05.036 PubMedCrossRefGoogle Scholar
  46. 46.
    Eggermann T (2010) Russell-Silver syndrome. Am J Med Genet C Semin Med Genet 154C(3):355–364. doi: 10.1002/ajmg.c.30274 PubMedCrossRefGoogle Scholar
  47. 47.
    Ekstrom TJ, Cui H, Li X, Ohlsson R (1995) Promoter-specific IGF2 imprinting status and its plasticity during human liver development. Development 121(2):309–316PubMedGoogle Scholar
  48. 48.
    El-Maarri O, Seoud M, Coullin P, Herbiniaux U, Oldenburg J, Rouleau G, Slim R (2003) Maternal alleles acquiring paternal methylation patterns in biparental complete hydatidiform moles. Hum Mol Genet 12(12):1405–1413PubMedCrossRefGoogle Scholar
  49. 49.
    Eloy P, Dehainault C, Sefta M, Aerts I, Doz F, Cassoux N, Lumbroso le Rouic L, Stoppa-Lyonnet D, Radvanyi F, Millot GA, Gauthier-Villars M, Houdayer C (2016) A Parent-of-Origin Effect Impacts the Phenotype in Low Penetrance Retinoblastoma Families Segregating the c.1981C>T/p.Arg661Trp Mutation of RB1. PLoS Genet 12(2):e1005888. doi: 10.1371/journal.pgen.1005888 PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Engel E (1980) A new genetic concept: uniparental disomy and its potential effect, isodisomy. Am J Med Genet 6(2):137–143. doi: 10.1002/ajmg.1320060207 PubMedCrossRefGoogle Scholar
  51. 51.
    Engel N, Thorvaldsen JL, Bartolomei MS (2006) CTCF binding sites promote transcription initiation and prevent DNA methylation on the maternal allele at the imprinted H19/Igf2 locus. Hum Mol Genet 15(19):2945–2954. doi: 10.1093/hmg/ddl237 PubMedCrossRefGoogle Scholar
  52. 52.
    Eriksson T, Frisk T, Gray SG, von Schweinitz D, Pietsch T, Larsson C, Sandstedt B, Ekström TJ (2001) Methylation changes in the human IGF2 p3 promoter parallel IGF2 expression in the primary tumor, established cell line, and xenograft of a human hepatoblastoma. Exp Cell Res 270(1):88–95. doi: 10.1006/excr.2001.5336 PubMedCrossRefGoogle Scholar
  53. 53.
    Feng W, Lu Z, Luo RZ, Zhang X, Seto E, Liao WS, Yu Y (2007) Multiple histone deacetylases repress tumor suppressor gene ARHI in breast cancer. Int J Cancer 120(8):1664–1668. doi: 10.1002/ijc.22474 PubMedCrossRefGoogle Scholar
  54. 54.
    Feng W, Marquez RT, Lu Z, Liu J, Lu KH, Issa JP, Fishman DM, Yu Y, Bast RC (2008) Imprinted tumor suppressor genes ARHI and PEG3 are the most frequently down-regulated in human ovarian cancers by loss of heterozygosity and promoter methylation. Cancer 112(7):1489–1502. doi: 10.1002/cncr.23323 PubMedCrossRefGoogle Scholar
  55. 55.
    Ferguson-Smith AC (2011) Genomic imprinting: the emergence of an epigenetic paradigm. Nat Rev Genet 12(8):565–575. doi: 10.1038/nrg3032 PubMedCrossRefGoogle Scholar
  56. 56.
    Fitzpatrick GV, Pugacheva EM, Shin JY, Abdullaev Z, Yang Y, Khatod K, Lobanenkov VV, Higgins MJ (2007) Allele-specific binding of CTCF to the multipartite imprinting control region KvDMR1. Mol Cell Biol 27(7):2636–2647. doi: 10.1128/MCB.02036-06 PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Fitzpatrick GV, Soloway PD, Higgins MJ (2002) Regional loss of imprinting and growth deficiency in mice with a targeted deletion of KvDMR1. Nat Genet 32(3):426–431. doi: 10.1038/ng988 PubMedCrossRefGoogle Scholar
  58. 58.
    Formosa A, Markert EK, Lena AM, Italiano D, Finazzi-Agro' E, Levine AJ, Bernardini S, Garabadgiu AV, Melino G, Candi E (2014) MicroRNAs, miR-154, miR-299-5p, miR-376a, miR-376c, miR-377, miR-381, miR-487b, miR-485-3p, miR-495 and miR-654-3p, mapped to the 14q32.31 locus, regulate proliferation, apoptosis, migration and invasion in metastatic prostate cancer cells. Oncogene 33(44):5173–5182. doi: 10.1038/onc.2013.451 PubMedCrossRefGoogle Scholar
  59. 59.
    Fujii S, Luo RZ, Yuan J, Kadota M, Oshimura M, Dent SR, Kondo Y, Issa JP, Bast RC, Yu Y (2003) Reactivation of the silenced and imprinted alleles of ARHI is associated with increased histone H3 acetylation and decreased histone H3 lysine 9 methylation. Hum Mol Genet 12(15):1791–1800PubMedCrossRefGoogle Scholar
  60. 60.
    Furukawa S, Haruta M, Arai Y, Honda S, Ohshima J, Sugawara W, Kageyama Y, Higashi Y, Nishida K, Tsunematsu Y, Nakadate H, Ishii M, Kaneko Y (2009) Yolk sac tumor but not seminoma or teratoma is associated with abnormal epigenetic reprogramming pathway and shows frequent hypermethylation of various tumor suppressor genes. Cancer Sci 100(4):698–708. doi: 10.1111/j.1349-7006.2009.01102.x PubMedCrossRefGoogle Scholar
  61. 61.
    Gadd S, Huff V, Huang CC, Ruteshouser EC, Dome JS, Grundy PE, Breslow N, Jennings L, Green DM, Beckwith JB, Perlman EJ (2012) Clinically relevant subsets identified by gene expression patterns support a revised ontogenic model of Wilms tumor: a Children's Oncology Group Study. Neoplasia 14(8):742–756PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Gejman R, Batista DL, Zhong Y, Zhou Y, Zhang X, Swearingen B, Stratakis CA, Hedley-Whyte ET, Klibanski A (2008) Selective loss of MEG3 expression and intergenic differentially methylated region hypermethylation in the MEG3/DLK1 locus in human clinically nonfunctioning pituitary adenomas. J Clin Endocrinol Metab 93(10):4119–4125. doi: 10.1210/jc.2007-2633 PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Ginno PA, Lott PL, Christensen HC, Korf I, Chédin F (2012) R-loop formation is a distinctive characteristic of unmethylated human CpG island promoters. Mol Cell 45(6):814–825. doi: 10.1016/j.molcel.2012.01.017
  64. 64.
    Gloss BS, Patterson KI, Barton CA, Gonzalez M, Scurry JP, Hacker NF, Sutherland RL, O'Brien PM, Clark SJ (2012) Integrative genome-wide expression and promoter DNA methylation profiling identifies a potential novel panel of ovarian cancer epigenetic biomarkers. Cancer Lett 318(1):76–85. doi: 10.1016/j.canlet.2011.12.003 PubMedCrossRefGoogle Scholar
  65. 65.
    Grbesa I, Ivkic M, Pegan B, Gall-Troselj K (2006) Loss of imprinting and promoter usage of the IGF2 in laryngeal squamous cell carcinoma. Cancer Lett 238(2):224–229. doi: 10.1016/j.canlet.2005.07.003 PubMedCrossRefGoogle Scholar
  66. 66.
    Gu TP, Guo F, Yang H, Wu HP, Xu GF, Liu W, Xie ZG, Shi L, He X, Jin SG, Iqbal K, Shi YG, Deng Z, Szabo PE, Pfeifer GP, Li J, Xu GL (2011) The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes. Nature 477(7366):606–610. doi: 10.1038/nature10443 PubMedCrossRefGoogle Scholar
  67. 67.
    Guo H, Tian T, Nan K, Wang W (2010) p57: A multifunctional protein in cancer (Review). Int J Oncol 36(6):1321–1329PubMedGoogle Scholar
  68. 68.
    Gururajan M, Josson S, Chu GC, Lu CL, Lu YT, Haga CL, Zhau HE, Liu C, Lichterman J, Duan P, Posadas EM, Chung LW (2014) miR-154* and miR-379 in the DLK1-DIO3 microRNA mega-cluster regulate epithelial to mesenchymal transition and bone metastasis of prostate cancer. Clin Cancer Res 20(24):6559–6569. doi: 10.1158/1078-0432.ccr-14-1784 PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Hagiwara K, Li Y, Kinoshita T, Kunishma S, Ohashi H, Hotta T, Nagai H (2010) Aberrant DNA methylation of the p57KIP2 gene is a sensitive biomarker for detecting minimal residual disease in diffuse large B cell lymphoma. Leuk Res 34(1):50–54. doi: 10.1016/j.leukres.2009.06.028 PubMedCrossRefGoogle Scholar
  70. 70.
    Hao Y, Crenshaw T, Moulton T, Newcomb E, Tycko B (1993) Tumour-suppressor activity of H19 RNA. Nature 365(6448):764–767. doi: 10.1038/365764a0 PubMedCrossRefGoogle Scholar
  71. 71.
    Hark AT, Schoenherr CJ, Katz DJ, Ingram RS, Levorse JM, Tilghman SM (2000) CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 locus. Nature 405(6785):486–489. doi: 10.1038/35013106 PubMedCrossRefGoogle Scholar
  72. 72.
    Hashimoto K, Azuma C, Tokugawa Y, Nobunaga T, Aki TA, Matsui Y, Yanagida T, Izumi H, Saji F, Murata Y (1997) Loss of H19 imprinting and up-regulation of H19 and SNRPN in a case with malignant mixed Müllerian tumor of the uterus. Hum Pathol 28(7):862–865PubMedCrossRefGoogle Scholar
  73. 73.
    Hayward BE, Barlier A, Korbonits M, Grossman AB, Jacquet P, Enjalbert A, Bonthron DT (2001) Imprinting of the G(s)alpha gene GNAS1 in the pathogenesis of acromegaly. J Clin Invest 107(6):R31–R36. doi: 10.1172/jci11887 PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Herold M, Bartkuhn M, Renkawitz R (2012) CTCF: insights into insulator function during development. Development 139(6):1045–1057. doi: 10.1242/dev.065268 PubMedCrossRefGoogle Scholar
  75. 75.
    Hibi K, Nakamura H, Hirai A, Fujikake Y, Kasai Y, Akiyama S, Ito K, Takagi H (1996) Loss of H19 imprinting in esophageal cancer. Cancer Res 56(3):480–482PubMedGoogle Scholar
  76. 76.
    Hiby SE, Lough M, Keverne EB, Surani MA, Loke YW, King A (2001) Paternal monoallelic expression of PEG3 in the human placenta. Hum Mol Genet 10(10):1093–1100PubMedCrossRefGoogle Scholar
  77. 77.
    Holm TM, Jackson-Grusby L, Brambrink T, Yamada Y, Rideout WM 3rd, Jaenisch R (2005) Global loss of imprinting leads to widespread tumorigenesis in adult mice. Cancer Cell 8(4):275–285. doi: 10.1016/j.ccr.2005.09.007 PubMedCrossRefGoogle Scholar
  78. 78.
    Honda S, Arai Y, Haruta M, Sasaki F, Ohira M, Yamaoka H, Horie H, Nakagawara A, Hiyama E, Todo S, Kaneko Y (2008) Loss of imprinting of IGF2 correlates with hypermethylation of the H19 differentially methylated region in hepatoblastoma. Br J Cancer 99(11):1891–1899. doi:10.1038/sj.bjc.6604754. Epub 2008 Oct 28Google Scholar
  79. 79.
    Huang GS, Brouwer-Visser J, Ramirez MJ, Kim CH, Hebert TM, Lin J, Arias-Pulido H, Qualls CR, Prossnitz ER, Goldberg GL, Smith HO, Horwitz SB (2010) Insulin-like growth factor 2 expression modulates Taxol resistance and is a candidate biomarker for reduced disease-free survival in ovarian cancer. Clin Cancer Res 16(11):2999–3010. doi: 10.1158/1078-0432.CCR-09-3233 PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Huang J, Lin Y, Li L, Qing D, Teng XM, Zhang YL, Hu X, Hu Y, Yang P, Han ZG (2009) ARHI, as a novel suppressor of cell growth and downregulated in human hepatocellular carcinoma, could contribute to hepatocarcinogenesis. Mol Carcinog 48(2):130–140. doi: 10.1002/mc.20461 PubMedCrossRefGoogle Scholar
  81. 81.
    Huang J, Zhang X, Zhang M, Zhu JD, Zhang YL, Lin Y, Wang KS, Qi XF, Zhang Q, Liu GZ, Yu J, Cui Y, Yang PY, Wang ZQ, Han ZG (2007) Up-regulation of DLK1 as an imprinted gene could contribute to human hepatocellular carcinoma. Carcinogenesis 28(5):1094–1103. doi: 10.1093/carcin/bgl215 PubMedCrossRefGoogle Scholar
  82. 82.
    Huang Y, Dai H, Guo QN (2012) TSSC3 overexpression reduces stemness and induces apoptosis of osteosarcoma tumor-initiating cells. Apoptosis 17(8):749–761. doi: 10.1007/s10495-012-0734-1 PubMedCrossRefGoogle Scholar
  83. 83.
    Huang Z, Wen Y, Shandilya R, Marks JR, Berchuck A, Murphy SK (2006) High throughput detection of M6P/IGF2R intronic hypermethylation and LOH in ovarian cancer. Nucleic Acids Res 34(2):555–563. doi: 10.1093/nar/gkj468 PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Ichikawa M, Arai Y, Haruta M, Furukawa S, Ariga T, Kajii T, Kaneko Y (2013) Meiosis error and subsequent genetic and epigenetic alterations invoke the malignant transformation of germ cell tumor. Genes Chromosomes Cancer 52(3):274–286. doi: 10.1002/gcc.22027 PubMedCrossRefGoogle Scholar
  85. 85.
    Ioannides Y, Lokulo-Sodipe K, Mackay DJ, Davies JH, Temple IK (2014) Temple syndrome: improving the recognition of an underdiagnosed chromosome 14 imprinting disorder: an analysis of 51 published cases. J Med Genet 51(8):495–501. doi: 10.1136/jmedgenet-2014-102396 PubMedCrossRefGoogle Scholar
  86. 86.
    Issa JP, Vertino PM, Boehm CD, Newsham IF, Baylin SB (1996) Switch from monoallelic to biallelic human IGF2 promoter methylation during aging and carcinogenesis. Proc Natl Acad Sci U S A 93(21):11757–11762PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Ito Y, Koessler T, Ibrahim AE, Rai S, Vowler SL, Abu-Amero S, Silva AL, Maia AT, Huddleston JE, Uribe-Lewis S, Woodfine K, Jagodic M, Nativio R, Dunning A, Moore G, Klenova E, Bingham S, Pharoah PD, Brenton JD, Beck S, Sandhu MS, Murrell A (2008) Somatically acquired hypomethylation of IGF2 in breast and colorectal cancer. Hum Mol Genet 17(17):2633–2643. doi: 10.1093/hmg/ddn163 PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Jacobs DI, Mao Y, Fu A, Kelly WK, Zhu Y (2013) Dysregulated methylation at imprinted genes in prostate tumor tissue detected by methylation microarray. BMC Urol 13:37. doi: 10.1186/1471-2490-13-37 PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Jin RJ, Lho Y, Wang Y, Ao M, Revelo MP, Hayward SW, Wills ML, Logan SK, Zhang P, Matusik RJ (2008) Down-regulation of p57Kip2 induces prostate cancer in the mouse. Cancer Res 68(10):3601–3608. doi: 10.1158/0008-5472.CAN-08-0073 PubMedCrossRefGoogle Scholar
  90. 90.
    Kagami M, Sekita Y, Nishimura G, Irie M, Kato F, Okada M, Yamamori S, Kishimoto H, Nakayama M, Tanaka Y, Matsuoka K, Takahashi T, Noguchi M, Tanaka Y, Masumoto K, Utsunomiya T, Kouzan H, Komatsu Y, Ohashi H, Kurosawa K, Kosaki K, Ferguson-Smith AC, Ishino F, Ogata T (2008) Deletions and epimutations affecting the human 14q32.2 imprinted region in individuals with paternal and maternal upd(14)-like phenotypes. Nat Genet 40(2):237–242. doi: 10.1038/ng.2007.56 PubMedCrossRefGoogle Scholar
  91. 91.
    Kamikihara T, Arima T, Kato K, Matsuda T, Kato H, Douchi T, Nagata Y, Nakao M, Wake N (2005) Epigenetic silencing of the imprinted gene ZAC by DNA methylation is an early event in the progression of human ovarian cancer. Int J Cancer 115(5):690–700. doi: 10.1002/ijc.20971 PubMedCrossRefGoogle Scholar
  92. 92.
    Kanber D, Berulava T, Ammerpohl O, Mitter D, Richter J, Siebert R, Horsthemke B, Lohmann D, Buiting K (2009) The human retinoblastoma gene is imprinted. PLoS Genet 5(12):e1000790. doi: 10.1371/journal.pgen.1000790 PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Kanduri C (2016) Long noncoding RNAs: Lessons from genomic imprinting. Biochim Biophys Acta 1859(1):102–111. doi: 10.1016/j.bbagrm.2015.05.006 PubMedCrossRefGoogle Scholar
  94. 94.
    Kanduri C, Fitzpatrick G, Mukhopadhyay R, Kanduri M, Lobanenkov V, Higgins M, Ohlsson R (2002) A differentially methylated imprinting control region within the Kcnq1 locus harbors a methylation-sensitive chromatin insulator. J Biol Chem 277(20):18106–18110. doi: 10.1074/jbc.M200031200 PubMedCrossRefGoogle Scholar
  95. 95.
    Kaneda A, Wang CJ, Cheong R, Timp W, Onyango P, Wen B, Iacobuzio-Donahue CA, Ohlsson R, Andraos R, Pearson MA, Sharov AA, Longo DL, Ko MS, Levchenko A, Feinberg AP (2007) Enhanced sensitivity to IGF-II signaling links loss of imprinting of IGF2 to increased cell proliferation and tumor risk. Proc Natl Acad Sci U S A 104(52):20926–20931. doi: 10.1073/pnas.0710359105 PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Kaneda M, Okano M, Hata K, Sado T, Tsujimoto N, Li E, Sasaki H (2004) Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting. Nature 429(6994):900–903. doi: 10.1038/nature02633 PubMedCrossRefGoogle Scholar
  97. 97.
    Kang L, Sun J, Wen X, Cui J, Wang G, Hoffman AR, Hu JF, Li W (2015) Aberrant allele-switch imprinting of a novel IGF1R intragenic antisense non-coding RNA in breast cancers. Eur J Cancer 51(2):260–270. doi: 10.1016/j.ejca.2014.10.031 PubMedCrossRefGoogle Scholar
  98. 98.
    Kavanagh E, Joseph B (2011) The hallmarks of CDKN1C (p57, KIP2) in cancer. Biochim Biophys Acta 1816(1):50–56. doi: 10.1016/j.bbcan.2011.03.002 PubMedGoogle Scholar
  99. 99.
    Kawakami T, Chano T, Minami K, Okabe H, Okada Y, Okamoto K (2006a) Imprinted DLK1 is a putative tumor suppressor gene and inactivated by epimutation at the region upstream of GTL2 in human renal cell carcinoma. Hum Mol Genet 15(6):821–830. doi: 10.1093/hmg/ddl001 PubMedCrossRefGoogle Scholar
  100. 100.
    Kawakami T, Zhang C, Okada Y, Okamoto K (2006b) Erasure of methylation imprint at the promoter and CTCF-binding site upstream of H19 in human testicular germ cell tumors of adolescents indicate their fetal germ cell origin. Oncogene 25(23):3225–3236. doi: 10.1038/sj.onc.1209362 PubMedCrossRefGoogle Scholar
  101. 101.
    Kelsey G (2010) Imprinting on chromosome 20: tissue-specific imprinting and imprinting mutations in the GNAS locus. Am J Med Genet C Semin Med Genet 154C(3):377–386. doi: 10.1002/ajmg.c.30271 PubMedCrossRefGoogle Scholar
  102. 102.
    Keniry A, Oxley D, Monnier P, Kyba M, Dandolo L, Smits G, Reik W (2012) The H19 lincRNA is a developmental reservoir of miR-675 that suppresses growth and Igf1r. Nat Cell Biol 14(7):659–665. doi: 10.1038/ncb2521 PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Kikuchi T, Toyota M, Itoh F, Suzuki H, Obata T, Yamamoto H, Kakiuchi H, Kusano M, Issa JP, Tokino T, Imai K (2002) Inactivation of p57KIP2 by regional promoter hypermethylation and histone deacetylation in human tumors. Oncogene 21(17):2741–2749. doi: 10.1038/sj.onc.1205376 PubMedCrossRefGoogle Scholar
  104. 104.
    Kim J, Bretz CL, Lee S (2015) Epigenetic instability of imprinted genes in human cancers. Nucleic Acids Res 43(22):10689–10699. doi: 10.1093/nar/gkv867 PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Kim SJ, Park SE, Lee C, Lee SY, Jo JH, Kim JM, Oh YK (2002) Alterations in promoter usage and expression levels of insulin-like growth factor-II and H19 genes in cervical carcinoma exhibiting biallelic expression of IGF-II. Biochim Biophys Acta 1586(3):307–315PubMedCrossRefGoogle Scholar
  106. 106.
    Kishino T, Lalande M, Wagstaff J (1997) UBE3A/E6-AP mutations cause Angelman syndrome. Nat Genet 15(1):70–73. doi: 10.1038/ng0197-70 PubMedCrossRefGoogle Scholar
  107. 107.
    Kobatake T, Yano M, Toyooka S, Tsukuda K, Dote H, Kikuchi T, Toyota M, Ouchida M, Aoe M, Date H, Pass HI, Doihara H, Shimizu N (2004) Aberrant methylation of p57KIP2 gene in lung and breast cancers and malignant mesotheliomas. Oncology reports 12(5):1087–1092PubMedGoogle Scholar
  108. 108.
    Kohda T, Asai A, Kuroiwa Y, Kobayashi S, Aisaka K, Nagashima G, Yoshida MC, Kondo Y, Kagiyama N, Kirino T, Kaneko-Ishino T, Ishino F (2001) Tumour suppressor activity of human imprinted gene PEG3 in a glioma cell line. Genes Cells 6(3):237–247PubMedCrossRefGoogle Scholar
  109. 109.
    Kondo M, Suzuki H, Ueda R, Osada H, Takagi K, Takahashi T, Takahashi T (1995) Frequent loss of imprinting of the H19 gene is often associated with its overexpression in human lung cancers. Oncogene 10(6):1193–1198PubMedGoogle Scholar
  110. 110.
    Kouzarides T (2007) Chromatin modifications and their function. Cell 128(4):693–705. doi: 10.1016/j.cell.2007.02.005 PubMedCrossRefGoogle Scholar
  111. 111.
    Kuang SQ, Ling X, Sanchez-Gonzalez B, Yang H, Andreeff M, Garcia-Manero G (2007) Differential tumor suppressor properties and transforming growth factor-beta responsiveness of p57KIP2 in leukemia cells with aberrant p57KIP2 promoter DNA methylation. Oncogene 26(10):1439–1448. doi: 10.1038/sj.onc.1209907 PubMedCrossRefGoogle Scholar
  112. 112.
    Kuerbitz SJ, Pahys J, Wilson A, Compitello N, Gray TA (2002) Hypermethylation of the imprinted NNAT locus occurs frequently in pediatric acute leukemia. Carcinogenesis 23(4):559–564PubMedCrossRefGoogle Scholar
  113. 113.
    Kurukuti S, Tiwari VK, Tavoosidana G, Pugacheva E, Murrell A, Zhao Z, Lobanenkov V, Reik W, Ohlsson R (2006) CTCF binding at the H19 imprinting control region mediates maternally inherited higher-order chromatin conformation to restrict enhancer access to Igf2. Proc Natl Acad Sci U S A 103(28):10684–10689. doi: 10.1073/pnas.0600326103 PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Lambert MP, Ancey PB, Esposti DD, Cros MP, Sklias A, Scoazec JY, Durantel D, Hernandez-Vargas H, Herceg Z (2015) Aberrant DNA methylation of imprinted loci in hepatocellular carcinoma and after in vitro exposure to common risk factors. Clin Epigenetics 7(1):15. doi: 10.1186/s13148-015-0053-9 PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Landis CA, Masters SB, Spada A, Pace AM, Bourne HR, Vallar L (1989) GTPase inhibiting mutations activate the alpha chain of Gs and stimulate adenylyl cyclase in human pituitary tumours. Nature 340(6236):692–696. doi: 10.1038/340692a0 PubMedCrossRefGoogle Scholar
  116. 116.
    Lee MH, Reynisdottir I, Massague J (1995) Cloning of p57KIP2, a cyclin-dependent kinase inhibitor with unique domain structure and tissue distribution. Genes Dev 9(6):639–649PubMedCrossRefGoogle Scholar
  117. 117.
    Lee SH, Appleby V, Jeyapalan JN, Palmer RD, Nicholson JC, Sottile V, Gao E, Coleman N, Scotting PJ (2011) Variable methylation of the imprinted gene, SNRPN, supports a relationship between intracranial germ cell tumours and neural stem cells. J Neurooncol 101(3):419–428. doi: 10.1007/s11060-010-0275-9 PubMedCrossRefGoogle Scholar
  118. 118.
    Lee SM, Lee EJ, Ko YH, Lee SH, Maeng L, Kim KM (2009) Prognostic significance of O6-methylguanine DNA methyltransferase and p57 methylation in patients with diffuse large B-cell lymphomas. APMIS 117(2):87–94. doi: 10.1111/j.1600-0463.2008.00017.x PubMedCrossRefGoogle Scholar
  119. 119.
    Lehner B, Kunz P, Saehr H, Fellenberg J (2014) Epigenetic silencing of genes and microRNAs within the imprinted Dlk1-Dio3 region at human chromosome 14.32 in giant cell tumor of bone. BMC Cancer 14:495. doi: 10.1186/1471-2407-14-495 PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    Lewis A, Mitsuya K, Umlauf D, Smith P, Dean W, Walter J, Higgins M, Feil R, Reik W (2004) Imprinting on distal chromosome 7 in the placenta involves repressive histone methylation independent of DNA methylation. Nat Genet 36(12):1291–1295. doi: 10.1038/ng1468 PubMedCrossRefGoogle Scholar
  121. 121.
    Li J, Bench AJ, Vassiliou GS, Fourouclas N, Ferguson-Smith AC, Green AR (2004) Imprinting of the human L3MBTL gene, a polycomb family member located in a region of chromosome 20 deleted in human myeloid malignancies. Proc Natl Acad Sci U S A 101(19):7341–7346. doi: 10.1073/pnas.0308195101 PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Li LL, Xue AM, Li BX, Shen YW, Li YH, Luo CL, Zhang MC, Jiang JQ, Xu ZD, Xie JH, Zhao ZQ (2014a) JMJD2A contributes to breast cancer progression through transcriptional repression of the tumor suppressor ARHI. Breast Cancer Res 16(3):R56. doi: 10.1186/bcr3667 PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Li T, Hu JF, Qiu X, Ling J, Chen H, Wang S, Hou A, Vu TH, Hoffman AR (2008a) CTCF regulates allelic expression of Igf2 by orchestrating a promoter-polycomb repressive complex 2 intrachromosomal loop. Mol Cell Biol 28(20):6473–6482. doi: 10.1128/MCB.00204-08 PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Li X, Cui H, Sandstedt B, Nordlinder H, Larsson E, Ekstrom TJ (1996) Expression levels of the insulin-like growth factor-II gene (IGF2) in the human liver: developmental relationships of the four promoters. J Endocrinol 149(1):117–124PubMedCrossRefGoogle Scholar
  125. 125.
    Li X, Ito M, Zhou F, Youngson N, Zuo X, Leder P, Ferguson-Smith AC (2008b) A maternal-zygotic effect gene, Zfp57, maintains both maternal and paternal imprints. Dev Cell 15(4):547–557. doi: 10.1016/j.devcel.2008.08.014 PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    Li X, Kogner P, Sandstedt B, Haas OA, Ekström TJ (1998) Promoter-specific methylation and expression alterations of Igf2 and H19 are involved in human hepatoblastoma. Int J Cancer 75(2):176–180Google Scholar
  127. 127.
    Li Y, Huang Y, Lv Y, Meng G, Guo QN (2014b) Epigenetic regulation of the pro-apoptosis gene TSSC3 in human osteosarcoma cells. Biomed Pharmacother 68(1):45–50. doi: 10.1016/j.biopha.2013.10.006 PubMedCrossRefGoogle Scholar
  128. 128.
    Li Y, Meng G, Guo QN (2008c) Changes in genomic imprinting and gene expression associated with transformation in a model of human osteosarcoma. Exp Mol Pathol 84(3):234–239. doi: 10.1016/j.yexmp.2008.03.013 PubMedCrossRefGoogle Scholar
  129. 129.
    Li Y, Meng G, Huang L, Guo QN (2009) Hypomethylation of the P3 promoter is associated with up-regulation of IGF2 expression in human osteosarcoma. Hum Pathol 40(10):1441–1447. doi: 10.1016/j.humpath.2009.03.003 PubMedCrossRefGoogle Scholar
  130. 130.
    Li Y, Nagai H, Ohno T, Yuge M, Hatano S, Ito E, Mori N, Saito H, Kinoshita T (2002) Aberrant DNA methylation of p57(KIP2) gene in the promoter region in lymphoid malignancies of B-cell phenotype. Blood 100(7):2572–2577. doi: 10.1182/blood-2001-11-0026 PubMedCrossRefGoogle Scholar
  131. 131.
    Kim JD, Kim H, Ekram MB, Yu S, Faulk C, Kim J (2011) Rex1/Zfp42 as an epigenetic regulator for genomic imprinting. Hum Mol Genet 20(7):1353–1362. doi: 10.1093/hmg/ddr017
  132. 132.
    Livingstone C (2013) IGF2 and cancer. Endocr Relat Cancer 20(6):R321–R339. doi: 10.1530/ERC-13-0231 PubMedCrossRefGoogle Scholar
  133. 133.
    Luo M, Li Z, Wang W, Zeng Y, Liu Z, Qiu J (2013) Long non-coding RNA H19 increases bladder cancer metastasis by associating with EZH2 and inhibiting E-cadherin expression. Cancer Lett 333(2):213–221. doi: 10.1016/j.canlet.2013.01.033 PubMedCrossRefGoogle Scholar
  134. 134.
    Luo RZ, Peng H, Xu F, Bao J, Pang Y, Pershad R, Issa JP, Liao WS, Bast RC, Yu Y (2001) Genomic structure and promoter characterization of an imprinted tumor suppressor gene ARHI. Biochim Biophys Acta 1519(3):216–222PubMedCrossRefGoogle Scholar
  135. 135.
    Lustig-Yariv O, Schulze E, Komitowski D, Erdmann V, Schneider T, de Groot N, Hochberg A (1997) The expression of the imprinted genes H19 and IGF-2 in choriocarcinoma cell lines. Is H19 a tumor suppressor gene? Oncogene 15(2):169–177. doi: 10.1038/sj.onc.1201175 PubMedCrossRefGoogle Scholar
  136. 136.
    Lv YF, Yan GN, Meng G, Zhang X, Guo QN (2015) Enhancer of zeste homolog 2 silencing inhibits tumor growth and lung metastasis in osteosarcoma. Sci Rep 5:12999. doi: 10.1038/srep12999 PubMedPubMedCentralCrossRefGoogle Scholar
  137. 137.
    Lynch CA, Tycko B, Bestor TH, Walsh CP (2002) Reactivation of a silenced H19 gene in human rhabdomyosarcoma by demethylation of DNA but not by histone hyperacetylation. Mol Cancer 1:2PubMedPubMedCentralCrossRefGoogle Scholar
  138. 138.
    Mackay DJ, Callaway JL, Marks SM, White HE, Acerini CL, Boonen SE, Dayanikli P, Firth HV, Goodship JA, Haemers AP, Hahnemann JM, Kordonouri O, Masoud AF, Oestergaard E, Storr J, Ellard S, Hattersley AT, Robinson DO, Temple IK (2008) Hypomethylation of multiple imprinted loci in individuals with transient neonatal diabetes is associated with mutations in ZFP57. Nat Genet 40(8):949–951. doi: 10.1038/ng.187 PubMedCrossRefGoogle Scholar
  139. 139.
    Mackay DJ, Temple IK (2010) Transient neonatal diabetes mellitus type 1. Am J Med Genet C Semin Med Genet 154C(3):335–342. doi: 10.1002/ajmg.c.30272 PubMedCrossRefGoogle Scholar
  140. 140.
    Maegawa S, Yoshioka H, Itaba N, Kubota N, Nishihara S, Shirayoshi Y, Nanba E, Oshimura M (2001) Epigenetic silencing of PEG3 gene expression in human glioma cell lines. Mol Carcinog 31(1):1–9PubMedCrossRefGoogle Scholar
  141. 141.
    Maeng YS, Choi HJ, Kwon JY, Park YW, Choi KS, Min JK, Kim YH, Suh PG, Kang KS, Won MH, Kim YM, Kwon YG (2009) Endothelial progenitor cell homing: prominent role of the IGF2-IGF2R-PLCbeta2 axis. Blood 113(1):233–243. doi: 10.1182/blood-2008-06-162891 PubMedCrossRefGoogle Scholar
  142. 142.
    Mancini-DiNardo D (2003) A differentially methylated region within the gene Kcnq1 functions as an imprinted promoter and silencer. Human Molecular Genetics 12(3):283–294. doi: 10.1093/hmg/ddg024
  143. 143.
    Mancini-Dinardo D, Steele SJ, Levorse JM, Ingram RS, Tilghman SM (2006) Elongation of the Kcnq1ot1 transcript is required for genomic imprinting of neighboring genes. Genes Dev 20(10):1268–1282. doi: 10.1101/gad.1416906 PubMedPubMedCentralCrossRefGoogle Scholar
  144. 144.
    Mantovani G (2011) Clinical review: Pseudohypoparathyroidism: diagnosis and treatment. J Clin Endocrinol Metab 96(10):3020–3030. doi: 10.1210/jc.2011-1048 PubMedCrossRefGoogle Scholar
  145. 145.
    Mantovani G, Bondioni S, Lania AG, Corbetta S, de Sanctis L, Cappa M, Di Battista E, Chanson P, Beck-Peccoz P, Spada A (2004) Parental origin of Gsalpha mutations in the McCune-Albright syndrome and in isolated endocrine tumors. J Clin Endocrinol Metab 89(6):3007–3009. doi: 10.1210/jc.2004-0194 PubMedCrossRefGoogle Scholar
  146. 146.
    Martinez R, Martin-Subero JI, Rohde V, Kirsch M, Alaminos M, Fernandez AF, Ropero S, Schackert G, Esteller M (2009) A microarray-based DNA methylation study of glioblastoma multiforme. Epigenetics 4(4):255–264PubMedCrossRefGoogle Scholar
  147. 147.
    Matouk IJ, DeGroot N, Mezan S, Ayesh S, Abu-lail R, Hochberg A, Galun E (2007) The H19 non-coding RNA is essential for human tumor growth. PLoS One 2(9):e845. doi: 10.1371/journal.pone.0000845 PubMedPubMedCentralCrossRefGoogle Scholar
  148. 148.
    Matsuoka S, Edwards MC, Bai C, Parker S, Zhang P, Baldini A, Harper JW, Elledge SJ (1995) p57KIP2, a structurally distinct member of the p21CIP1 Cdk inhibitor family, is a candidate tumor suppressor gene. Genes Dev 9(6):650–662PubMedCrossRefGoogle Scholar
  149. 149.
    Matsuura T, Takahashi K, Nakayama K, Kobayashi T, Choi-Miura NH, Tomita M, Kanayama N (2002) Increased expression of vascular endothelial growth factor in placentas of p57(Kip2) null embryos. FEBS Lett 532(3):283–288PubMedCrossRefGoogle Scholar
  150. 150.
    McGrath J, Solter D (1984) Completion of mouse embryogenesis requires both the maternal and paternal genomes. Cell 37(1):179–183PubMedCrossRefGoogle Scholar
  151. 151.
    Menigatti M, Staiano T, Manser CN, Bauerfeind P, Komljenovic A, Robinson M, Jiricny J, Buffoli F, Marra G (2013) Epigenetic silencing of monoallelically methylated miRNA loci in precancerous colorectal lesions. Oncogenesis 2:e56. doi: 10.1038/oncsis.2013.21 PubMedPubMedCentralCrossRefGoogle Scholar
  152. 152.
    Mohammad F, Mondal T, Guseva N, Pandey GK, Kanduri C (2010) Kcnq1ot1 noncoding RNA mediates transcriptional gene silencing by interacting with Dnmt1. Development 137(15):2493–2499. doi: 10.1242/dev.048181 PubMedCrossRefGoogle Scholar
  153. 153.
    Monk D (2015) Germline-derived DNA methylation and early embryo epigenetic reprogramming: The selected survival of imprints. Int J Biochem Cell Biol 67:128–138. doi: 10.1016/j.biocel.2015.04.014 PubMedCrossRefGoogle Scholar
  154. 154.
    Ito Y, Maehara K, Kaneki E, Matsuoka K, Sugahara N, Miyata T, Kamura H, Yamaguchi Y, Kono A, Nakabayashi K, Migita O, Higashimoto K, Soejima H, Okamoto A, Nakamura H, Kimura T, Wake N, Taniguchi T, Hata K (2016) Novel Nonsense Mutation in the NLRP7 Gene Associated with Recurrent Hydatidiform Mole. Gynecol Obstet Invest 81(4):353–358. doi: 10.1159/000441780
  155. 155.
    Moulton T, Crenshaw T, Hao Y, Moosikasuwan J, Lin N, Dembitzer F, Hensle T, Weiss L, McMorrow L, Loew T et al (1994) Epigenetic lesions at the H19 locus in Wilms' tumour patients. Nat Genet 7(3):440–447. doi: 10.1038/ng0794-440 PubMedCrossRefGoogle Scholar
  156. 156.
    Murakami K, Oshimura M, Kugoh H (2007) Suggestive evidence for chromosomal localization of non-coding RNA from imprinted LIT1. J Hum Genet 52(11):926–933. doi: 10.1007/s10038-007-0196-4 PubMedCrossRefGoogle Scholar
  157. 157.
    Murata A, Baba Y, Watanabe M, Shigaki H, Miyake K, Ishimoto T, Iwatsuki M, Iwagami S, Yoshida N, Oki E, Morita M, Nakao M, Baba H (2014) IGF2 DMR0 methylation, loss of imprinting, and patient prognosis in esophageal squamous cell carcinoma. Ann Surg Oncol 21(4):1166–1174. doi: 10.1245/s10434-013-3414-7 PubMedCrossRefGoogle Scholar
  158. 158.
    Murphy SK, Huang Z, Wen Y, Spillman MA, Whitaker RS, Simel LR, Nichols TD, Marks JR, Berchuck A (2006) Frequent IGF2/H19 domain epigenetic alterations and elevated IGF2 expression in epithelial ovarian cancer. Mol Cancer Res 4(4):283–292. doi: 10.1158/1541-7786.MCR-05-0138 PubMedCrossRefGoogle Scholar
  159. 159.
    Murphy SK, Wylie AA, Jirtle RL (2001) Imprinting of PEG3, the human homologue of a mouse gene involved in nurturing behavior. Genomics 71(1):110–117. doi: 10.1006/geno.2000.6419 PubMedCrossRefGoogle Scholar
  160. 160.
    Murrell A (2006) Genomic imprinting and cancer: from primordial germ cells to somatic cells. ScientificWorldJournal 6:1888–1910. doi: 10.1100/tsw.2006.318 PubMedCrossRefGoogle Scholar
  161. 161.
    Murrell A, Heeson S, Reik W (2004) Interaction between differentially methylated regions partitions the imprinted genes Igf2 and H19 into parent-specific chromatin loops. Nat Genet 36(8):889–893. doi: 10.1038/ng1402 PubMedCrossRefGoogle Scholar
  162. 162.
    Murrell A, Ito Y, Verde G, Huddleston J, Woodfine K, Silengo MC, Spreafico F, Perotti D, De Crescenzo A, Sparago A, Cerrato F, Riccio A (2008) Distinct methylation changes at the IGF2-H19 locus in congenital growth disorders and cancer. PLoS One 3(3):e1849. doi: 10.1371/journal.pone.0001849 PubMedPubMedCentralCrossRefGoogle Scholar
  163. 163.
    Mussa A, Molinatto C, Baldassarre G, Riberi E, Russo S, Larizza L, Riccio A, Ferrero GB (2016a) Cancer Risk in Beckwith-Wiedemann Syndrome: A Systematic Review and Meta-Analysis Outlining a Novel (Epi)Genotype Specific Histotype Targeted Screening Protocol. J Pediatr. 176:142–149.e1. doi: 10.1016/j.jpeds.2016.05.038 PubMedCrossRefGoogle Scholar
  164. 164.
    Mussa A, Russo S, De Crescenzo A, Freschi A, Calzari L, Maitz S, Macchiaiolo M, Molinatto C, Baldassarre G, Mariani M, Tarani L, Bedeschi MF, Milani D, Melis D, Bartuli A, Cubellis MV, Selicorni A, Cirillo Silengo M, Larizza L, Riccio A, Ferrero GB (2016b) (Epi)genotype-phenotype correlations in Beckwith-Wiedemann syndrome. Eur J Hum Genet 24(2):183–190. doi: 10.1038/ejhg.2015.88 PubMedCrossRefGoogle Scholar
  165. 165.
    Nakagawa H, Chadwick RB, Peltomaki P, Plass C, Nakamura Y, de La Chapelle A (2001) Loss of imprinting of the insulin-like growth factor II gene occurs by biallelic methylation in a core region of H19-associated CTCF-binding sites in colorectal cancer. Proc Natl Acad Sci U S A 98(2):591–596. doi: 10.1073/pnas.011528698 PubMedCrossRefGoogle Scholar
  166. 166.
    Nakamura T, Liu YJ, Nakashima H, Umehara H, Inoue K, Matoba S, Tachibana M, Ogura A, Shinkai Y, Nakano T (2012) PGC7 binds histone H3K9me2 to protect against conversion of 5mC to 5hmC in early embryos. Nature 486(7403):415–419. doi: 10.1038/nature11093 PubMedGoogle Scholar
  167. 167.
    Nakano S, Murakami K, Meguro M, Soejima H, Higashimoto K, Urano T, Kugoh H, Mukai T, Ikeguchi M, Oshimura M (2006) Expression profile of LIT1/KCNQ1OT1 and epigenetic status at the KvDMR1 in colorectal cancers. Cancer Sci 97(11):1147–1154. doi: 10.1111/j.1349-7006.2006.00305.x PubMedCrossRefGoogle Scholar
  168. 168.
    Nativio R, Sparago A, Ito Y, Weksberg R, Riccio A, Murrell A (2011) Disruption of genomic neighbourhood at the imprinted IGF2-H19 locus in Beckwith-Wiedemann syndrome and Silver-Russell syndrome. Hum Mol Genet 20(7):1363–1374. doi: 10.1093/hmg/ddr018 PubMedPubMedCentralCrossRefGoogle Scholar
  169. 169.
    Nativio R, Wendt KS, Ito Y, Huddleston JE, Uribe-Lewis S, Woodfine K, Krueger C, Reik W, Peters JM, Murrell A (2009) Cohesin is required for higher-order chromatin conformation at the imprinted IGF2-H19 locus. PLoS Genet 5(11):e1000739. doi: 10.1371/journal.pgen.1000739 PubMedPubMedCentralCrossRefGoogle Scholar
  170. 170.
    Nicholls RD, Knoll JH, Butler MG, Karam S, Lalande M (1989) Genetic imprinting suggested by maternal heterodisomy in nondeletion Prader-Willi syndrome. Nature 342(6247):281–285. doi: 10.1038/342281a0 PubMedCrossRefGoogle Scholar
  171. 171.
    Nielsen HM, How-Kit A, Guerin C, Castinetti F, Vollan HK, De Micco C, Daunay A, Taieb D, Van Loo P, Besse C, Kristensen VN, Hansen LL, Barlier A, Sebag F, Tost J (2015) Copy number variations alter methylation and parallel IGF2 overexpression in adrenal tumors. Endocr Relat Cancer 22(6):953–967. doi: 10.1530/erc-15-0086 PubMedPubMedCentralCrossRefGoogle Scholar
  172. 172.
    Niemczyk M, Ito Y, Huddleston J, Git A, Abu-Amero S, Caldas C, Moore GE, Stojic L, Murrell A (2013) Imprinted chromatin around DIRAS3 regulates alternative splicing of GNG12-AS1, a long noncoding RNA. Am J Hum Genet 93(2):224–235. doi: 10.1016/j.ajhg.2013.06.010 PubMedPubMedCentralCrossRefGoogle Scholar
  173. 173.
    Ogata T, Kagami M (2016) Kagami-Ogata syndrome: a clinically recognizable upd(14)pat and related disorder affecting the chromosome 14q32.2 imprinted region. J Hum Genet 61(2):87–94. doi: 10.1038/jhg.2015.113 PubMedCrossRefGoogle Scholar
  174. 174.
    Ogawa O, Eccles MR, Szeto J, McNoe LA, Yun K, Maw MA, Smith PJ, Reeve AE (1993) Relaxation of insulin-like growth factor II gene imprinting implicated in Wilms' tumour. Nature 362(6422):749–751. doi: 10.1038/362749a0 PubMedCrossRefGoogle Scholar
  175. 175.
    Ohtsuka Y, Higashimoto K, Oka T, Yatsuki H, Jozaki K, Maeda T, Kawahara K, Hamasaki Y, Matsuo M, Nishioka K, Joh K, Mukai T, Soejima H (2016) Identification of consensus motifs associated with mitotic recombination and clinical characteristics in patients with paternal uniparental isodisomy of chromosome 11. Hum Mol Genet 25(7):1406–1419. doi: 10.1093/hmg/ddw023 PubMedCrossRefGoogle Scholar
  176. 176.
    Ooi SK, Qiu C, Bernstein E, Li K, Jia D, Yang Z, Erdjument-Bromage H, Tempst P, Lin SP, Allis CD, Cheng X, Bestor TH (2007) DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA. Nature 448(7154):714–717. doi: 10.1038/nature05987 PubMedPubMedCentralCrossRefGoogle Scholar
  177. 177.
    Otsuka S, Maegawa S, Takamura A, Kamitani H, Watanabe T, Oshimura M, Nanba E (2009) Aberrant promoter methylation and expression of the imprinted PEG3 gene in glioma. Proc Jpn Acad Ser B Phys Biol Sci 85(4):157–165PubMedPubMedCentralCrossRefGoogle Scholar
  178. 178.
    Pandey RR, Mondal T, Mohammad F, Enroth S, Redrup L, Komorowski J, Nagano T, Mancini-Dinardo D, Kanduri C (2008) Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation. Mol Cell 32(2):232–246. doi: 10.1016/j.molcel.2008.08.022 PubMedCrossRefGoogle Scholar
  179. 179.
    Paradowska A, Fenic I, Konrad L, Sturm K, Wagenlehner F, Weidner W, Steger K (2009) Aberrant epigenetic modifications in the CTCF binding domain of the IGF2/H19 gene in prostate cancer compared with benign prostate hyperplasia. Int J Oncol 35(1):87–96PubMedCrossRefGoogle Scholar
  180. 180.
    Parry DA, Logan CV, Hayward BE, Shires M, Landolsi H, Diggle C, Carr I, Rittore C, Touitou I, Philibert L, Fisher RA, Fallahian M, Huntriss JD, Picton HM, Malik S, Taylor GR, Johnson CA, Bonthron DT, Sheridan EG (2011) Mutations causing familial biparental hydatidiform mole implicate c6orf221 as a possible regulator of genomic imprinting in the human oocyte. Am J Hum Genet 89(3):451–458. doi: 10.1016/j.ajhg.2011.08.002 PubMedPubMedCentralCrossRefGoogle Scholar
  181. 181.
    Peters J (2014) The role of genomic imprinting in biology and disease: an expanding view. Nat Rev Genet 15(8):517–530. doi: 10.1038/nrg3766 PubMedCrossRefGoogle Scholar
  182. 182.
    Picard C, Silvy M, Gerard C, Buffat C, Lavaque E, Figarella-Branger D, Dufour H, Gabert J, Beckers A, Brue T, Enjalbert A, Barlier A (2007) Gs alpha overexpression and loss of Gs alpha imprinting in human somatotroph adenomas: association with tumor size and response to pharmacologic treatment. Int J Cancer 121(6):1245–1252. doi: 10.1002/ijc.22816 PubMedCrossRefGoogle Scholar
  183. 183.
    Piecewicz SM, Pandey A, Roy B, Xiang SH, Zetter BR, Sengupta S (2012) Insulin-like growth factors promote vasculogenesis in embryonic stem cells. PLoS One 7(2):e32191. doi: 10.1371/journal.pone.0032191 PubMedPubMedCentralCrossRefGoogle Scholar
  184. 184.
    Pike BL, Greiner TC, Wang X, Weisenburger DD, Hsu YH, Renaud G, Wolfsberg TG, Kim M, Weisenberger DJ, Siegmund KD, Ye W, Groshen S, Mehrian-Shai R, Delabie J, Chan WC, Laird PW, Hacia JG (2008) DNA methylation profiles in diffuse large B-cell lymphoma and their relationship to gene expression status. Leukemia 22(5):1035–1043. doi: 10.1038/leu.2008.18 PubMedPubMedCentralCrossRefGoogle Scholar
  185. 185.
    Poirier K, Chalas C, Tissier F, Couvert P, Mallet V, Carrié A, Marchio A, Sarli D, Gicquel C, Chaussade S, Beljord C, Chelly J, Kerjean A, Terris B (2003) Loss of parental-specific methylation at the IGF2 locus in human hepatocellular carcinoma. J Pathol 201(3):473–479. doi: 10.1002/path.1477 PubMedCrossRefGoogle Scholar
  186. 186.
    Quenneville S, Verde G, Corsinotti A, Kapopoulou A, Jakobsson J, Offner S, Baglivo I, Pedone PV, Grimaldi G, Riccio A, Trono D (2011) In embryonic stem cells, ZFP57/KAP1 recognize a methylated hexanucleotide to affect chromatin and DNA methylation of imprinting control regions. Mol Cell 44(3):361–372. doi: 10.1016/j.molcel.2011.08.032 PubMedPubMedCentralCrossRefGoogle Scholar
  187. 187.
    Rainier S, Johnson LA, Dobry CJ, Ping AJ, Grundy PE, Feinberg AP (1993) Relaxation of imprinted genes in human cancer. Nature 362(6422):747–749. doi: 10.1038/362747a0 PubMedCrossRefGoogle Scholar
  188. 188.
    Ravenel JD, Broman KW, Perlman EJ, Niemitz EL, Jayawardena TM, Bell DW, Haber DA, Uejima H, Feinberg AP (2001) Loss of imprinting of insulin-like growth factor-II (IGF2) gene in distinguishing specific biologic subtypes of Wilms tumor. J Natl Cancer Inst 93(22):1698–1703PubMedCrossRefGoogle Scholar
  189. 189.
    Revill K, Dudley KJ, Clayton RN, McNicol AM, Farrell WE (2009) Loss of neuronatin expression is associated with promoter hypermethylation in pituitary adenoma. Endocr Relat Cancer 16(2):537–548. doi: 10.1677/erc-09-0008 PubMedCrossRefGoogle Scholar
  190. 190.
    Riemenschneider MJ, Reifenberger J, Reifenberger G (2008) Frequent biallelic inactivation and transcriptional silencing of the DIRAS3 gene at 1p31 in oligodendroglial tumors with 1p loss. Int J Cancer 122(11):2503–2510. doi: 10.1002/ijc.23409 PubMedCrossRefGoogle Scholar
  191. 191.
    Rijlaarsdam MA, Tax DM, Gillis AJ, Dorssers LC, Koestler DC, de Ridder J, Looijenga LH (2015) Genome wide DNA methylation profiles provide clues to the origin and pathogenesis of germ cell tumors. PLoS One 10(4):e0122146. doi: 10.1371/journal.pone.0122146 PubMedPubMedCentralCrossRefGoogle Scholar
  192. 192.
    Riordan JD, Keng VW, Tschida BR, Scheetz TE, Bell JB, Podetz-Pedersen KM, Moser CD, Copeland NG, Jenkins NA, Roberts LR, Largaespada DA, Dupuy AJ (2013) Identification of rtl1, a retrotransposon-derived imprinted gene, as a novel driver of hepatocarcinogenesis. PLoS Genet 9(4):e1003441. doi: 10.1371/journal.pgen.1003441 PubMedPubMedCentralCrossRefGoogle Scholar
  193. 193.
    Robson JE, Eaton SA, Underhill P, Williams D, Peters J (2012) MicroRNAs 296 and 298 are imprinted and part of the GNAS/Gnas cluster and miR-296 targets IKBKE and Tmed9. RNA 18(1):135–144. doi: 10.1261/rna.029561.111 PubMedPubMedCentralCrossRefGoogle Scholar
  194. 194.
    Rodriguez BA, Weng YI, Liu TM, Zuo T, Hsu PY, Lin CH, Cheng AL, Cui H, Yan PS, Huang TH (2011) Estrogen-mediated epigenetic repression of the imprinted gene cyclin-dependent kinase inhibitor 1C in breast cancer cells. Carcinogenesis 32(6):812–821. doi: 10.1093/carcin/bgr017 PubMedPubMedCentralCrossRefGoogle Scholar
  195. 195.
    Romanelli V, Nakabayashi K, Vizoso M, Moran S, Iglesias-Platas I, Sugahara N, Simón C, Hata K, Esteller M, Court F, Monk D (2014) Variable maternal methylation overlapping the nc886/vtRNA2-1 locus is locked between hypermethylated repeats and is frequently altered in cancer. Epigenetics 9(5):783–790. doi: 10.4161/epi.28323 PubMedPubMedCentralCrossRefGoogle Scholar
  196. 196.
    Rumbajan JM, Maeda T, Souzaki R, Mitsui K, Higashimoto K, Nakabayashi K, Yatsuki H, Nishioka K, Harada R, Aoki S, Kohashi K, Oda Y, Hata K, Saji T, Taguchi T, Tajiri T, Soejima H, Joh K (2013) Comprehensive analyses of imprinted differentially methylated regions reveal epigenetic and genetic characteristics in hepatoblastoma. BMC Cancer 13:608. doi: 10.1186/1471-2407-13-608 PubMedPubMedCentralCrossRefGoogle Scholar
  197. 197.
    Saal HM (1993) Russell-Silver syndrome. In: Pagon RA, Adam MP, Ardinger HH et al (eds) GeneReviews®. University of Washington, Seattle, WAGoogle Scholar
  198. 198.
    Sahoo T, del Gaudio D, German JR, Shinawi M, Peters SU, Person RE, Garnica A, Cheung SW, Beaudet AL (2008) Prader-Willi phenotype caused by paternal deficiency for the HBII-85 C/D box small nucleolar RNA cluster. Nat Genet 40(6):719–721. doi: 10.1038/ng.158 PubMedPubMedCentralCrossRefGoogle Scholar
  199. 199.
    Sakatani T, Kaneda A, Iacobuzio-Donahue CA, Carter MG, de Boom WS, Okano H, Ko MS, Ohlsson R, Longo DL, Feinberg AP (2005) Loss of imprinting of Igf2 alters intestinal maturation and tumorigenesis in mice. Science 307(5717):1976–1978. doi: 10.1126/science.1108080 PubMedCrossRefGoogle Scholar
  200. 200.
    Sanchez-Delgado M, Martin-Trujillo A, Tayama C, Vidal E, Esteller M, Iglesias-Platas I, Deo N, Barney O, Maclean K, Hata K, Nakabayashi K, Fisher R, Monk D (2015) Absence of Maternal Methylation in Biparental Hydatidiform Moles from Women with NLRP7 Maternal-Effect Mutations Reveals Widespread Placenta-Specific Imprinting. PLoS Genet 11(11):e1005644. doi: 10.1371/journal.pgen.1005644 PubMedPubMedCentralCrossRefGoogle Scholar
  201. 201.
    Satoh Y, Nakadate H, Nakagawachi T, Higashimoto K, Joh K, Masaki Z, Uozumi J, Kaneko Y, Mukai T, Soejima H (2006) Genetic and epigenetic alterations on the short arm of chromosome 11 are involved in a majority of sporadic Wilms' tumours. Br J Cancer 95(4):541–547. doi: 10.1038/sj.bjc.6603302 PubMedPubMedCentralCrossRefGoogle Scholar
  202. 202.
    Savage SA, Woodson K, Walk E, Modi W, Liao J, Douglass C, Hoover RN, Chanock SJ, Group NOES (2007) Analysis of genes critical for growth regulation identifies Insulin-like Growth Factor 2 Receptor variations with possible functional significance as risk factors for osteosarcoma. Cancer Epidemiol Biomarkers Prev 16(8):1667–1674. doi: 10.1158/1055-9965.epi-07-0214 PubMedCrossRefGoogle Scholar
  203. 203.
    Saxena A (2003) The Product of the Imprinted Gene IPL Marks Human Villous Cytotrophoblast and is Lost in Complete Hydatidiform Mole. Placenta 24(8-9):835–842. doi: 10.1016/s0143-4004(03)00130-9 PubMedCrossRefGoogle Scholar
  204. 204.
    Scelfo RA, Schwienbacher C, Veronese A, Gramantieri L, Bolondi L, Querzoli P, Nenci I, Calin GA, Angioni A, Barbanti-Brodano G, Negrini M (2002) Loss of methylation at chromosome 11p15.5 is common in human adult tumors. Oncogene 21(16):2564–2572. doi: 10.1038/sj.onc.1205336 PubMedCrossRefGoogle Scholar
  205. 205.
    Schoenherr CJ, Levorse JM, Tilghman SM (2003) CTCF maintains differential methylation at the Igf2/H19 locus. Nat Genet 33(1):66–69. doi: 10.1038/ng1057 PubMedCrossRefGoogle Scholar
  206. 206.
    Schwienbacher C, Angioni A, Scelfo R, Veronese A, Calin GA, Massazza G, Hatada I, Barbanti-Brodano G, Negrini M (2000) Abnormal RNA expression of 11p15 imprinted genes and kidney developmental genes in Wilms' tumor. Cancer Res 60(6):1521–1525PubMedGoogle Scholar
  207. 207.
    Shen L, Toyota M, Kondo Y, Obata T, Daniel S, Pierce S, Imai K, Kantarjian HM, Issa JP, Garcia-Manero G (2003) Aberrant DNA methylation of p57KIP2 identifies a cell-cycle regulatory pathway with prognostic impact in adult acute lymphocytic leukemia. Blood 101(10):4131–4136. doi: 10.1182/blood-2002-08-2466 PubMedCrossRefGoogle Scholar
  208. 208.
    Shuman C, Beckwith JB, Smith AC, Weksberg R (1993) Beckwith-Wiedemann syndrome. In: Pagon RA, Adam MP, Ardinger HH et al (eds) GeneReviews®. University of Washington, Seattle, WAGoogle Scholar
  209. 209.
    Soejima H, Higashimoto K (2013) Epigenetic and genetic alterations of the imprinting disorder Beckwith-Wiedemann syndrome and related disorders. J Hum Genet 58(7):402–409. doi: 10.1038/jhg.2013.51 PubMedCrossRefGoogle Scholar
  210. 210.
    Soejima H, Nakagawachi T, Zhao W, Higashimoto K, Urano T, Matsukura S, Kitajima Y, Takeuchi M, Nakayama M, Oshimura M, Miyazaki K, Joh K, Mukai T (2004) Silencing of imprinted CDKN1C gene expression is associated with loss of CpG and histone H3 lysine 9 methylation at DMR-LIT1 in esophageal cancer. Oncogene 23(25):4380–4388. doi: 10.1038/sj.onc.1207576 PubMedCrossRefGoogle Scholar
  211. 211.
    Steenman MJ, Rainier S, Dobry CJ, Grundy P, Horon IL, Feinberg AP (1994) Loss of imprinting of IGF2 is linked to reduced expression and abnormal methylation of H19 in Wilms' tumour. Nat Genet 7(3):433–439. doi: 10.1038/ng0794-433 PubMedCrossRefGoogle Scholar
  212. 212.
    Sullivan MJ, Taniguchi T, Jhee A, Kerr N, Reeve AE (1999) Relaxation of IGF2 imprinting in Wilms tumours associated with specific changes in IGF2 methylation. Oncogene 18(52):7527–7534. doi: 10.1038/sj.onc.1203096 PubMedCrossRefGoogle Scholar
  213. 213.
    Sun Y, Gao D, Liu Y, Huang J, Lessnick S, Tanaka S (2006) IGF2 is critical for tumorigenesis by synovial sarcoma oncoprotein SYT-SSX1. Oncogene 25(7):1042–1052. doi: 10.1038/sj.onc.1209143 PubMedCrossRefGoogle Scholar
  214. 214.
    Surani MA, Barton SC, Norris ML (1984) Development of reconstituted mouse eggs suggests imprinting of the genome during gametogenesis. Nature 308(5959):548–550PubMedCrossRefGoogle Scholar
  215. 215.
    Takai D, Gonzales FA, Tsai YC, Thayer MJ, Jones PA (2001) Large scale mapping of methylcytosines in CTCF-binding sites in the human H19 promoter and aberrant hypomethylation in human bladder cancer. Hum Mol Genet 10(23):2619–2626PubMedCrossRefGoogle Scholar
  216. 216.
    Temple IK, Mackay DJG, Docherty LE (1993) Diabetes mellitus, 6q24-related transient neonatal. In: Pagon RA, Adam MP, Ardinger HH et al (eds) GeneReviews®. University of Washington, Seattle, WAGoogle Scholar
  217. 217.
    Terranova R, Yokobayashi S, Stadler MB, Otte AP, van Lohuizen M, Orkin SH, Peters AH (2008) Polycomb group proteins Ezh2 and Rnf2 direct genomic contraction and imprinted repression in early mouse embryos. Dev Cell 15(5):668–679. doi: 10.1016/j.devcel.2008.08.015 PubMedCrossRefGoogle Scholar
  218. 218.
    Thakur N, Kanduri M, Holmgren C, Mukhopadhyay R, Kanduri C (2003) Bidirectional silencing and DNA methylation-sensitive methylation-spreading properties of the Kcnq1 imprinting control region map to the same regions. J Biol Chem 278(11):9514–9519. doi: 10.1074/jbc.M212203200 PubMedCrossRefGoogle Scholar
  219. 219.
    Thakur N, Tiwari VK, Thomassin H, Pandey RR, Kanduri M, Gondor A, Grange T, Ohlsson R, Kanduri C (2004) An antisense RNA regulates the bidirectional silencing property of the Kcnq1 imprinting control region. Mol Cell Biol 24(18):7855–7862. doi: 10.1128/MCB.24.18.7855-7862.2004 PubMedPubMedCentralCrossRefGoogle Scholar
  220. 220.
    Tomizawa S, Sasaki H (2012) Genomic imprinting and its relevance to congenital disease, infertility, molar pregnancy and induced pluripotent stem cell. J Hum Genet 57(2):84–91. doi: 10.1038/jhg.2011.151 PubMedCrossRefGoogle Scholar
  221. 221.
    Tsang WP, Ng EK, Ng SS, Jin H, Yu J, Sung JJ, Kwok TT (2010) Oncofetal H19-derived miR-675 regulates tumor suppressor RB in human colorectal cancer. Carcinogenesis 31(3):350–358. doi: 10.1093/carcin/bgp181 PubMedCrossRefGoogle Scholar
  222. 222.
    Turan S, Bastepe M (2015) GNAS Spectrum of Disorders. Curr Osteoporos Rep 13(3):146–158. doi: 10.1007/s11914-015-0268-x PubMedPubMedCentralCrossRefGoogle Scholar
  223. 223.
    Ulaner GA, Vu TH, Li T, Hu JF, Yao XM, Yang Y, Gorlick R, Meyers P, Healey J, Ladanyi M, Hoffman AR (2003) Loss of imprinting of IGF2 and H19 in osteosarcoma is accompanied by reciprocal methylation changes of a CTCF-binding site. Hum Mol Genet 12(5):535–549PubMedCrossRefGoogle Scholar
  224. 224.
    Valleley EM, Cordery SF, Carr IM, MacLennan KA, Bonthron DT (2010) Loss of expression of ZAC/PLAGL1 in diffuse large B-cell lymphoma is independent of promoter hypermethylation. Genes Chromosomes Cancer 49(5):480–486. doi: 10.1002/gcc.20758 PubMedGoogle Scholar
  225. 225.
    Verkerk AJ, Ariel I, Dekker MC, Schneider T, van Gurp RJ, de Groot N, Gillis AJ, Oosterhuis JW, Hochberg AA, Looijenga LH (1997) Unique expression patterns of H19 in human testicular cancers of different etiology. Oncogene 14(1):95–107. doi: 10.1038/sj.onc.1200802 PubMedCrossRefGoogle Scholar
  226. 226.
    Vlachos P, Joseph B (2009) The Cdk inhibitor p57(Kip2) controls LIM-kinase 1 activity and regulates actin cytoskeleton dynamics. Oncogene 28(47):4175–4188. doi: 10.1038/onc.2009.269 PubMedCrossRefGoogle Scholar
  227. 227.
    Vlachos P, Nyman U, Hajji N, Joseph B (2007) The cell cycle inhibitor p57(Kip2) promotes cell death via the mitochondrial apoptotic pathway. Cell Death Differ 14(8):1497–1507. doi: 10.1038/sj.cdd.4402158 PubMedCrossRefGoogle Scholar
  228. 228.
    Vu TH, Hoffman A (1996) Alterations in the promoter-specific imprinting of the insulin-like growth factor-II gene in Wilms' tumor. J Biol Chem 271(15):9014–9023PubMedCrossRefGoogle Scholar
  229. 229.
    Vu TH, Hoffman AR (1994) Promoter-specific imprinting of the human insulin-like growth factor-II gene. Nature 371(6499):714–717. doi: 10.1038/371714a0 PubMedCrossRefGoogle Scholar
  230. 230.
    Wagschal A, Sutherland HG, Woodfine K, Henckel A, Chebli K, Schulz R, Oakey RJ, Bickmore WA, Feil R (2008) G9a histone methyltransferase contributes to imprinting in the mouse placenta. Mol Cell Biol 28(3):1104–1113. doi: 10.1128/MCB.01111-07 PubMedCrossRefGoogle Scholar
  231. 231.
    Wang P, Ren Z, Sun P (2012) Overexpression of the long non-coding RNA MEG3 impairs in vitro glioma cell proliferation. J Cell Biochem 113(6):1868–1874. doi: 10.1002/jcb.24055 PubMedCrossRefGoogle Scholar
  232. 232.
    Wang X, Li G, Koul S, Ohki R, Maurer M, Borczuk A, Halmos B (2015) PHLDA2 is a key oncogene-induced negative feedback inhibitor of EGFR/ErbB2 signaling via interference with AKT signaling. Oncotarget. doi: 10.18632/oncotarget.3674
  233. 233.
    Weber F, Aldred MA, Morrison CD, Plass C, Frilling A, Broelsch CE, Waite KA, Eng C (2005) Silencing of the maternally imprinted tumor suppressor ARHI contributes to follicular thyroid carcinogenesis. J Clin Endocrinol Metab 90(2):1149–1155. doi: 10.1210/jc.2004-1447 PubMedCrossRefGoogle Scholar
  234. 234.
    Wei JJ, Wu X, Peng Y, Shi G, Basturk O, Olca B, Yang X, Daniels G, Osman I, Ouyang J, Hernando E, Pellicer A, Rhim JS, Melamed J, Lee P (2011) Regulation of HMGA1 expression by microRNA-296 affects prostate cancer growth and invasion. Clin Cancer Res 17(6):1297–1305. doi: 10.1158/1078-0432.ccr-10-0993 PubMedCrossRefGoogle Scholar
  235. 235.
    Wendt KS, Yoshida K, Itoh T, Bando M, Koch B, Schirghuber E, Tsutsumi S, Nagae G, Ishihara K, Mishiro T, Yahata K, Imamoto F, Aburatani H, Nakao M, Imamoto N, Maeshima K, Shirahige K, Peters JM (2008) Cohesin mediates transcriptional insulation by CCCTC-binding factor. Nature 451(7180):796–801. doi: 10.1038/nature06634 PubMedCrossRefGoogle Scholar
  236. 236.
    Wossidlo M, Nakamura T, Lepikhov K, Marques CJ, Zakhartchenko V, Boiani M, Arand J, Nakano T, Reik W, Walter J (2011) 5-Hydroxymethylcytosine in the mammalian zygote is linked with epigenetic reprogramming. Nat Commun 2:241. doi: 10.1038/ncomms1240 PubMedCrossRefGoogle Scholar
  237. 237.
    Wu J, Qin Y, Li B, He WZ, Sun ZL (2008) Hypomethylated and hypermethylated profiles of H19DMR are associated with the aberrant imprinting of IGF2 and H19 in human hepatocellular carcinoma. Genomics 91(5):443–450. doi: 10.1016/j.ygeno.2008.01.007 PubMedCrossRefGoogle Scholar
  238. 238.
    Xiong Y, Fang JH, Yun JP, Yang J, Zhang Y, Jia WH, Zhuang SM (2010) Effects of microRNA-29 on apoptosis, tumorigenicity, and prognosis of hepatocellular carcinoma. Hepatology 51(3):836–845. doi: 10.1002/hep.23380 PubMedGoogle Scholar
  239. 239.
    Xu W, Fan H, He X, Zhang J, Xie W (2006) LOI of IGF2 is associated with esophageal cancer and linked to methylation status of IGF2 DMR. J Exp Clin Cancer Res 25(4):543–547PubMedGoogle Scholar
  240. 240.
    Yan L, Zhou J, Gao Y, Ghazal S, Lu L, Bellone S, Yang Y, Liu N, Zhao X, Santin AD, Taylor H, Huang Y (2015) Regulation of tumor cell migration and invasion by the H19/let-7 axis is antagonized by metformin-induced DNA methylation. Oncogene 34(23):3076–3084. doi: 10.1038/onc.2014.236 PubMedCrossRefGoogle Scholar
  241. 241.
    Yang F, Bi J, Xue X, Zheng L, Zhi K, Hua J, Fang G (2012) Up-regulated long non-coding RNA H19 contributes to proliferation of gastric cancer cells. FEBS J 279(17):3159–3165. doi: 10.1111/j.1742-4658.2012.08694.x PubMedCrossRefGoogle Scholar
  242. 242.
    Yang X, Karuturi RK, Sun F, Aau M, Yu K, Shao R, Miller LD, Tan PB, Yu Q (2009) CDKN1C (p57) is a direct target of EZH2 and suppressed by multiple epigenetic mechanisms in breast cancer cells. PLoS One 4(4):e5011. doi: 10.1371/journal.pone.0005011 PubMedPubMedCentralCrossRefGoogle Scholar
  243. 243.
    Yoon YS, Jeong S, Rong Q, Park KY, Chung JH, Pfeifer K (2007) Analysis of the H19ICR insulator. Mol Cell Biol 27(9):3499–3510. doi: 10.1128/MCB.02170-06 PubMedPubMedCentralCrossRefGoogle Scholar
  244. 244.
    Yoshimizu T, Miroglio A, Ripoche MA, Gabory A, Vernucci M, Riccio A, Colnot S, Godard C, Terris B, Jammes H, Dandolo L (2008) The H19 locus acts in vivo as a tumor suppressor. Proc Natl Acad Sci U S A 105(34):12417–12422. doi: 10.1073/pnas.0801540105 PubMedPubMedCentralCrossRefGoogle Scholar
  245. 245.
    Yu J, Li A, Hong SM, Hruban RH, Goggins M (2012) MicroRNA alterations of pancreatic intraepithelial neoplasias. Clin Cancer Res 18(4):981–992. doi: 10.1158/1078-0432.ccr-11-2347 PubMedCrossRefGoogle Scholar
  246. 246.
    Yu Y, Xu F, Peng H, Fang X, Zhao S, Li Y, Cuevas B, Kuo WL, Gray JW, Siciliano M, Mills GB, Bast RC (1999) NOEY2 (ARHI), an imprinted putative tumor suppressor gene in ovarian and breast carcinomas. Proc Natl Acad Sci U S A 96(1):214–219PubMedPubMedCentralCrossRefGoogle Scholar
  247. 247.
    Yuan E, Li CM, Yamashiro DJ, Kandel J, Thaker H, Murty VV, Tycko B (2005) Genomic profiling maps loss of heterozygosity and defines the timing and stage dependence of epigenetic and genetic events in Wilms' tumors. Mol Cancer Res 3(9):493–502. doi: 10.1158/1541-7786.mcr-05-0082 PubMedCrossRefGoogle Scholar
  248. 248.
    Yuan J, Luo RZ, Fujii S, Wang L, Hu W, Andreeff M, Pan Y, Kadota M, Oshimura M, Sahin AA, Issa JP, Bast RC, Yu Y (2003) Aberrant methylation and silencing of ARHI, an imprinted tumor suppressor gene in which the function is lost in breast cancers. Cancer Res 63(14):4174–4180Google Scholar
  249. 249.
    Zhang A, Skaar DA, Li Y, Huang D, Price TM, Murphy SK, Jirtle RL (2011) Novel retrotransposed imprinted locus identified at human 6p25. Nucleic Acids Res 39(13):5388–5400. doi: 10.1093/nar/gkr108
  250. 250.
    Zhang X, Gejman R, Mahta A, Zhong Y, Rice KA, Zhou Y, Cheunsuchon P, Louis DN, Klibanski A (2010) Maternally expressed gene 3, an imprinted noncoding RNA gene, is associated with meningioma pathogenesis and progression. Cancer Res 70(6):2350–2358. doi: 10.1158/0008-5472.CAN-09-3885
  251. 251.
    Zhang X, Zhou Y, Mehta KR, Danila DC, Scolavino S, Johnson SR, Klibanski A (2003) A pituitary-derived MEG3 isoform functions as a growth suppressor in tumor cells. J Clin Endocrinol Metab 88(11):5119–5126. doi: 10.1210/jc.2003-030222
  252. 252.
    Zhao J, Dahle D, Zhou Y, Zhang X, Klibanski A (2005) Hypermethylation of the promoter region is associated with the loss of MEG3 gene expression in human pituitary tumors. J Clin Endocrinol Metab 90(4):2179–2186. doi: 10.1210/jc.2004-1848

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Ken Higashimoto
    • 1
  • Keiichiro Joh
    • 1
  • Hidenobu Soejima
    • 1
  1. 1.Division of Molecular Genetics & Epigenetics, Department of Biomolecular SciencesSaga UniversitySagaJapan

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