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Genetics of the hamartomatous polyposis syndromes: a molecular review

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Abstract

Background and aims

Hamartomatous polyposis syndromes are a heterogeneous group of disorders that are inherited in an autosomal dominant fashion. These syndromes only represent a small number of the inherited gastrointestinal cancer predisposition syndromes. However, many of these syndromes carry a substantial risk for developing colorectal cancer, as well as extra-colonic malignancy.

Materials and methods

We searched for articles on inherited hamartomatous polyposis syndromes, including familial juvenile polyposis syndrome, Peutz–Jeghers syndrome, PTEN hamartoma tumor syndrome, multiple endocrine neoplasia syndrome 2B, hereditary mixed polyposis syndrome, Cronkhite–Canada syndrome, basal cell nevus syndrome, and neurofibromatosis 1, in PubMed, Embase, and Elsevier ScienceDirect. In this review, we briefly discuss the diagnosis and clinical features of these disorders and the molecular alterations responsible for these syndromes.

Results and conclusion

Given the clinical similarities of these hamartomatous syndromes and the autosomal dominant pattern of inheritance, it is sometimes difficult to differentiate hamartomatous polyps, especially with atypical presentation. The molecular analysis and diagnosis make it possible to identify the subtype of these syndromes. In addition, these tests raise an intriguing possibility that surveillance and early medical intervention will allow for the identification of at-risk patients and the reduction of morbidity and mortality.

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References

  1. Nagy R, Sweet K, Eng C (2004) Highly penetrant hereditary cancer syndromes. Oncogene 23(38):6445–6470

    Article  PubMed  CAS  Google Scholar 

  2. Attard TM, Abraham SC, Cuffari C (2003) The clinical spectrum of duodenal polyps in pediatrics. J Pediatr Gastroenterol Nutr 36(1):116–119

    Article  PubMed  CAS  Google Scholar 

  3. Wirtzfield DA, Petrelli NJ, Rodriguez-Bigas MA (2001) Hamartomatous polyposis syndromes: molecular genetics, neoplastic risk and surveillance recommendations. Ann Surg Oncol 8(4):319–327

    Article  Google Scholar 

  4. Zbuk KM, Eng C (2007) Hamartomatous polyposis syndromes. Nature Clinical Practice Gastroenterology & Hepatology 4(9):492–502

    CAS  Google Scholar 

  5. Gatalica Z, Torlakovic E (2008) Pathology of the hereditary colorectal carcinoma. Fam Cancer 7(1):15–26

    Article  PubMed  Google Scholar 

  6. Sachatello CR, Hahn IS, Carrington CB (1974) Juvenile gastrointestinal polyposis in a female infant: report of a case and review of the literature of a recently recognized syndrome. Surgery 75(1):107–114

    PubMed  CAS  Google Scholar 

  7. Jass JR, Williams CB, Bussey HJ, Morson BC (1988) Juvenile polyposis—a precancerous condition. Histopathology 13(6):619–630

    PubMed  CAS  Google Scholar 

  8. Giardiello FM, Hamilton SR, Kern SE, Offerhaus GJ, Green PA, Celano P, Krush AJ, Booker SV (1991) Colorectal neoplasia in juvenile polyposis or juvenile polyps. Arch Dis Child 66(8):971–975

    Article  PubMed  CAS  Google Scholar 

  9. Attard TM, Young RJ (2006) Diagnosis and management of gastrointestinal polyps. Gastroenterol Nurs 29(1):16–22

    Article  PubMed  Google Scholar 

  10. Howe JR, Sayed MG, Ahmed AF, Ringold J, Larsen-Haidle J, Merg A, Mitros FA, Vaccaro CA, Petersen GM, Giardiello FM, Tinley ST, Aaltonen LA, Lynch HT (2004) The prevalence of MADH4 and BMPR1A mutations in juvenile polyposis and absence of BMPR2, BMPR1B, and ACVR1 mutations. J Med Genet 41(7):484–491

    Article  PubMed  CAS  Google Scholar 

  11. Heldin C-H, Miyazono K, ten Dijke P (1997) TGF-β signalling from cell membrane to nucleus through SMAD proteins. Nature 390(6659):465–471

    Article  PubMed  CAS  Google Scholar 

  12. Sweet K, Willis J, Zhou XP, Gallione C, Sawada T, Alhopuro P, Khoo SK, Patocs A, Martin C, Bridgeman S, Heinz J, Pilarski R, Lehtonen R, Prior TW, Frebourg T, Teh BT, Marchuk DA, Aaltonen LA, Eng C (2005) Molecular classification of patients with unexplained hamartomatous and hyperplastic polyposis. JAMA 294(19):2465–2473

    Article  PubMed  CAS  Google Scholar 

  13. Howe J, Haidle JL, Lal G, Bair J, Song C, Pechman B, Chinnathambi S, Lynch HT (2007) ENG mutations in MADH4/BMPR1A mutation negative patients with juvenile polyposis. Clin Genet 71(1):91–92

    Article  PubMed  CAS  Google Scholar 

  14. Waite KA, Eng C (2003) From developmental disorder to heritable cancer: it’s all in the BMP/TGF-beta family. Nat Rev Genet 4(10):763–773

    Article  PubMed  CAS  Google Scholar 

  15. Grady WM, Markowitz SD (2002) Genetic and epigenetic alterations in colon cancer. Annu Rev Genomics Hum Genet. 3:101–128

    Article  PubMed  CAS  Google Scholar 

  16. Sayed MG, Ahmed AF, Ringold JR, Anderson ME, Bair JL, Mitros FA, Lynch HT, Tinley ST, Petersen GM, Giardiello FM, Vogelstein B, Howe JR (2002) Germline SMAD4 or BMPR1A mutations and phenotype of juvenile polyposis. Ann Surg Onco 9(9):901–906

    Article  CAS  Google Scholar 

  17. Friedl W, Uhlhaas S, Schulmann K, Stolte M, Loff S, Back W, Mangold E, Stern M, Knaebel HP, Sutter C, Weber RG, Pistorius S, Burger B, Propping P (2002) Juvenile polyposis: massive gastric polyposis is more common in MADH4 mutation carriers than in BMPR1A mutation carriers. Hum Genet 111(1):108–111

    Article  PubMed  CAS  Google Scholar 

  18. Gallione CJ, Repetto GM, Legius E, Rustgi AK, Schelley SL, Tejpar S, Mitchell G, Drouin E, Westermann CJ, Marchuk DA (2004) A combined syndrome of juvenile polyposis and hereditary haemorrhagic telangiectasia associated with mutations in MADH4 (SMAD4). Lancet 363(9412):852–859

    Article  PubMed  CAS  Google Scholar 

  19. Woodford-Richens K, Williamson J, Bevan S, Young J, Leggett B, Frayling I, Thway Y, Hodgson S, Kim JC, Iwama T, Novelli M, Sheer D, Poulsom R, Wright N, Houlston R, Tomlinson I (2000) Allelic loss at SMAD4 in polyps from juvenile polyposis patients and use of fluorescence in situ hybridization to demonstrate clonal origin of the epithelium. Cancer Res 60(9):2477–2482

    PubMed  CAS  Google Scholar 

  20. Woodford-Richens KL, Rowan AJ, Poulsom R, Bevan S, Salovaara R, Aaltonen LA, Houlston RS, Wright NA, Tomlinson IP (2001) Comprehensive analysis of SMAD4mutations and protein expression in juvenile polyposis. Evidence for a distinct genetic pathway and polyp morphology in SMAD4 mutation carriers. Am J Pathol 159(4):1293–1300

    PubMed  CAS  Google Scholar 

  21. Howe JR, Bair JL, Sayed MG, Anderson ME, Mitros FA, Petersen GM, Velculescu VE, Traverso G, Vogelstein B (2001) Germline mutations of the gene encoding bone morphogenetic protein receptor 1A in juvenile polyposis. Nat Genet 28(2):184–187

    Article  PubMed  CAS  Google Scholar 

  22. Zhou XP, Woodford-Richens K, Lehtonen R, Kurose K, Aldred M, Hampel H, Launonen V, Virta S, Pilarski R, Salovaara R, Bodmer WF, Conrad BA, Dunlop M, Hodgson SV, Iwama T, Järvinen H, Kellokumpu I, Kim JC, Leggett B, Markie D, Mecklin JP, Neale K, Phillips R, Piris J, Rozen P, Houlston RS, Aaltonen LA, Tomlinson IP, Eng C (2001) Germline mutations in BMPR1A/ALK3 cause a subset of cases of juvenile polyposis syndrome and of Cowden and Bannayan–Riley–Ruvalcaba syndromes. Am J Hum Genet 69(4):704–711

    Article  PubMed  CAS  Google Scholar 

  23. Eng C (2001) To be or not to BMP. Nat Genet 28(2):105–107

    Article  PubMed  CAS  Google Scholar 

  24. Delnatte C, Sanlaville D, Mougenot JF, Vermeesch JR, Houdayer C, Blois MC, Genevieve D, Goulet O, Fryns JP, Jaubert F, Vekemans M, Lyonnet S, Romana S, Eng C, Stoppa-Lyonnet D (2006) Contiguous gene deletion within chromosome arm 10q is associated with juvenile polyposis of infancy, reflecting cooperation between the BMPR1A and PTEN tumor-suppressor genes. Am J Hum Genet 78(6):1066–1074

    Article  PubMed  CAS  Google Scholar 

  25. Tsuchiya KD, Wiesner G, Cassidy SB, Limwongse C, Boyle JT, Schwartz S (1998) Deletion 10q23.2–q23.33 in a patient with gastrointestinal juvenile polyposis and other features of a Cowden-like syndrome. Genes Chromosomes Cancer 21(2):113–118

    Article  PubMed  CAS  Google Scholar 

  26. Jacoby RF, Schlack S, Sekhon G, Laxova R (1997) Del(10)(q22.3q24.1) associated with juvenile polyposis. Am J Med Genet 70(4):361–364

    Article  PubMed  CAS  Google Scholar 

  27. Lynch HT, Lynch JF, Lynch PM, Attard T (2008) Hereditary colorectal cancer syndromes: molecular genetics, genetic counseling, diagnosis and management. Familial Cancer 7(1):27–39

    Article  PubMed  CAS  Google Scholar 

  28. Takaku K, Miyoshi H, Matsunaga A, Oshima M, Sasaki N, Taketo MM (1999) Gastric and duodenal polyps in Smad4 (Dpc4) knockout mice. Cancer Res 59(24):6113–6117

    PubMed  CAS  Google Scholar 

  29. Mishina Y, Suzuki A, Ueno N, Behringer RR (1995) Bmpr encodes a type I bone morphogenetic protein receptor that is essential for gastrulation during mouse embryogenesis. Genes Dev 9(24):3027–3037

    Article  PubMed  CAS  Google Scholar 

  30. Bourdeau A, Dumont DJ, Letarte M (1999) A murine model of hereditary hemorrhagic telangiectasia. J Clin Invest 104(10):1343–1351

    Article  PubMed  CAS  Google Scholar 

  31. He XC, Zhang J, Tong WG, Tawfik O, Ross J, Scoville DH, Tian Q, Zeng X, He X, Wiedemann LM et al (2004) BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-beta-catenin signaling. Nat Genet 36:1117–1121

    Article  PubMed  CAS  Google Scholar 

  32. Hardwick JC, Kodach LL, Offerhaus GJ, van den Brink GR (2008) Bone morphogenetic protein signalling in colorectal cancer. Nat Rev Cancer 8(10):806–812

    Article  PubMed  CAS  Google Scholar 

  33. Wu TT, Rezai B, Rashid A, Luce MC, Cayouette MC, Kim C, Sani N, Mishra L, Moskaluk CA, Yardley JH, Hamilton SR (1997) Genetic alterations and epithelial dysplasia in juvenile polyposis syndrome and sporadic juvenile polyps. Am J Pathol 150(3):939–947

    PubMed  CAS  Google Scholar 

  34. Winship IM, Dudding TE (2008) Lessons from the skin—cutaneous features of familial cancer. Lancet Oncol 9(5):462–472

    Article  PubMed  Google Scholar 

  35. Bourke B, Broderick A, Bohane T (2006) Peutz–Jeghers syndrome and management recommendations. Clin Gastroenterol Hepatol 4(12):1550

    Article  PubMed  Google Scholar 

  36. McGarrity TJ, Amos C (2006) Peutz–Jeghers syndrome: clinicopathology and molecular alterations. Cell Mol Life Sci 63(18):2135–2144

    Article  PubMed  CAS  Google Scholar 

  37. Hemminki A, Markie D, Tomlinson I, Avizienyte E, Roth S, Loukola A, Bignell G, Warren W, Aminoff M, Höglund P, Järvinen H, Kristo P, Pelin K, Ridanpää M, Salovaara R, Toro T, Bodmer W, Olschwang S, Olsen AS, Stratton MR, de la Chapelle A, Aaltonen LA (1998) A serine/threonine kinase gene defective in Peutz–Jeghers syndrome. Nature 391(6663):184–187

    Article  PubMed  CAS  Google Scholar 

  38. Alessi DR, Sakamoto K, Bayascas JR (2006) LKB1-dependent signaling pathways. Annu Rev Biochem 75:137–163

    Article  PubMed  CAS  Google Scholar 

  39. Corradetti MN, Inoki K, Bardeesy N, DePinho RA, Guan KL (2004) Regulation of the TSC pathway by LKB1: evidence of a molecular link between tuberous sclerosis complex and Peutz–Jeghers syndrome. Genes Dev 18(13):1533–1538

    Article  PubMed  CAS  Google Scholar 

  40. Volikos E, Robinson J, Aittomäki K, Mecklin JP, Järvinen H, Westerman AM, de Rooji FW, Vogel T, Moeslein G, Launonen V, Tomlinson IP, Silver AR, Aaltonen LA (2006) LKB1 exonic and whole gene deletions are a common cause of Peutz–Jeghers syndrome. J Med Genet 43(5):e18

    Article  PubMed  CAS  Google Scholar 

  41. Giardiello FM, Brensinger JD, Tersmette AC, Goodman SN, Petersen GM, Booker SV, Cruz-Correa M, Offerhaus JA (2000) Very high risk of cancer in familial Peutz–Jeghers syndrome. Gastroenterology 119(6):1447–1453

    Article  PubMed  CAS  Google Scholar 

  42. Amos CI, Keitheri-Cheteri MB, Sabripour M, Wei C, McGarrity TJ, Seldin MF, Nations L, Lynch PM, Fidder HH, Friedman E, Frazier ML (2004) Genotype–phenotype correlations in Peutz–Jeghers syndrome. J Med Genet 41(5):327–333

    Article  PubMed  CAS  Google Scholar 

  43. Lim W, Olschwang S, Keller JJ, Westerman AM, Menko FH, Boardman LA, Scott RJ, Trimbath J, Giardiello FM, Gruber SB, Gille JJ, Offerhaus GJ, de Rooij FW, Wilson JH, Spigelman AD, Phillips RK, Houlston RS (2004) Relative frequency and morphology of cancers in STK11 mutation carriers. Gastroenterology 126(7):1788–1794

    Article  PubMed  CAS  Google Scholar 

  44. Cetta F, Dhamo A (2007) Inherited multitumoral syndromes including colorectal carcinoma. Surg Oncol 16(Suppl 1):S17–S23

    Article  PubMed  Google Scholar 

  45. Yoon KA, Ku JL, Choi HS, Heo SC, Jeong SY, Park YJ, Kim NK, Kim JC, Jung PM, Park Jg (2000) Germline mutations of the gene in Korean Peutz–Jeghers syndrome patients. Br J Cancer 82(8):1403–1406

    PubMed  CAS  Google Scholar 

  46. Miyoshi H, Nakau M, Ishikawa TO, Seldin MF, Oshima M, Taketo MM (2002) Gastrointestinal hamartomatous polyposis in Lkb1 heterozygous knockout mice. Cancer Res 62(8):2261–2266

    PubMed  CAS  Google Scholar 

  47. Hearle N, Schumacher V, Menko FH, Olschwang S, Boardman LA, Gille JJ, Keller JJ, Westerman AM, Scott RJ, Lim W, Trimbath JD, Giardiello FM, Gruber SB, Offerhaus GJ, de Rooij FW, Wilson JH, Hansmann A, Möslein G, Royer-Pokora B, Vogel T, Phillips RK, Spigelman AD, Houlston RS (2006) Frequency and spectrum of cancers in the Peutz–Jeghers syndrome. Clin Cancer Res 12(10):3209–15

    Article  PubMed  CAS  Google Scholar 

  48. Eng C (2000) Will the real Cowden syndrome please stand up: revised diagnostic criteria. J Med Genet 37(11):828–830

    Article  PubMed  CAS  Google Scholar 

  49. Gorlin RJ, Cohen MM, Condon LM, Burke BA (1992) Bannayan–Riley–Ruvalcaba syndrome. Am J Med Genet 44(3):307–314

    Article  PubMed  CAS  Google Scholar 

  50. Wiedemann HR, Burgio GR, Aldenhoff P, Kunze J, Kaufmann HJ, Schirg E (1983) The Proteus syndrome. Partial gigantism of the hands and/or feet, nevi, hemihypertrophy, subcutaneous tumors, macrocephaly or other skull anomalies and possible accelerated growth and visceral affections. Eur J Pediatr 140(1):5–12

    Article  PubMed  CAS  Google Scholar 

  51. Marsh DJ, Kum JB, Lunetta KL, Bennett MJ, Gorlin RJ, Ahmed SF, Bodurtha J, Crowe C, Curtis MA, Dasouki M, Dunn T, Feit H, Geraghty MT, Graham JM Jr, Hodgson SV, Hunter A, Korf BR, Manchester D, Miesfeldt S, Murday VA, Nathanson KL, Parisi M, Pober B, Romano C, Eng C (1999) PTEN mutation spectrum and genotypephenotype correlations in Bannayan–Riley–Ruvalcaba syndrome suggest a single entity with Cowden syndrome. Human Molec Genet 8(8):1461–1472

    Article  CAS  Google Scholar 

  52. Zhou XP, Waite KA, Pilarski R, Hampel H, Fernandez MJ, Bos C, Dasouki M, Feldman GL, Greenberg LA, Ivanovich J, Matloff E, Patterson A, Pierpont ME, Russo D, Nassif NT, Eng C (2003) Germline PTEN promoter mutations and deletions in Cowden/Bannayan–Riley–Ruvalcaba syndrome result in aberrant PTEN protein and dysregulation of the phosphoinositol-3-kinase/Akt pathway. Am J Hum Genet 73(2):404–411

    Article  PubMed  CAS  Google Scholar 

  53. McGarrity TJ, Wagner Baker MJ, Ruggiero FM, Thiboutot DM, Hampel H, Zhou XP, Eng C (2003) GI polyposis and glycogenic acanthosis of the esophagus associated with PTEN mutation positive Cowden syndrome in the absence of cutaneous manifestations. Am J Gastroenterol 98(6):1429–1434

    Article  PubMed  Google Scholar 

  54. Chow LM, Baker SJ (2006) PTEN function in normal and neoplastic growth. Cancer Lett 241(2):184–196

    Article  PubMed  CAS  Google Scholar 

  55. Zbuk KM, Eng C (2007) Cancer phenomics: RET and PTEN as illustrative models. Nat Rev Cancer 7(1):35–45

    Article  PubMed  CAS  Google Scholar 

  56. Suzuki A, de la Pompa JL, Stambolic V, Elia AJ, Sasaki T, del Barco Barrantes I, Ho A, Wakeham A, Itie A, Khoo W, Fukumoto M, Mak TW (1998) High cancer susceptibility and embryonic lethality associated with mutation of the PTEN tumor suppressor gene in mice. Curr Biol 8(21):1169–1178

    Article  PubMed  CAS  Google Scholar 

  57. Schreibman IR, Baker M, Amos C, McGarrity TJ (2005) The hamartomatous polyposis syndromes: a clinical and molecular review. Am J Gastroenterol 100(2):476–490

    Article  PubMed  Google Scholar 

  58. Eng C, Smith DP, Mulligan LM, Nagai MA, Healey CS, Ponder MA, Gardner E, Scheumann GF, Jackson CE, Tunnacliffe A (1994) Point mutation within the tyrosine kinase domain of the RET proto-oncogene in multiple endocrine neoplasia type 2B and related sporadic tumours. Hum Mol Genet 3(2):237–241

    Article  PubMed  CAS  Google Scholar 

  59. Miyauchi A, Futami H, Hai N, Yokozawa T, Kuma K, Aoki N, Kosugi S, Sugano K, Yamaguchi K (1999) Two germline missense mutations at codons 804 and 806 of the RET proto-oncogene in the same allele in a patient with multiple endocrine neoplasia type 2B without codon 918 mutation. Jpn J Cancer Res 90(1):1–5

    PubMed  CAS  Google Scholar 

  60. Carlson KM, Bracamontes J, Jackson CE, Clark R, Lacroix A, Wells SA Jr, Goodfellow PJ (1994) Parent-of-origin effects in multiple endocrine neoplasia type 2B. Am J Hum Genet 55(6):1076–1082

    PubMed  CAS  Google Scholar 

  61. Manié S, Santoro M, Fusco A, Billaud M (2001) The RET receptor: function in development and dysfunction in congenital malformation. Trends Genet 17(10):580–589

    Article  PubMed  Google Scholar 

  62. Whitelaw SC, Murday VA, Tomlinson IP, Thomas HJ, Cottrell S, Ginsberg A, Bukofzer S, Hodgson SV, Skudowitz RB, Jass JR, Talbot IC, Northover JM, Bodmer WF, Solomon E (1997) Clinical and molecular features of the hereditary mixed polyposis syndrome. Gastroenterology 112(2):327–334

    Article  PubMed  CAS  Google Scholar 

  63. Rozen P, Samuel Z, Brazowski E (2003) A prospective study of the clinical, genetic, screening, and pathologic features of a family with hereditary mixed polyposis syndrome. Am J Gastroenterol 98(10):2317–2320

    Article  PubMed  CAS  Google Scholar 

  64. Thomas HJ, Whitelaw SC, Cottrell SE, Murday VA, Tomlinson IP, Markie D, Jones T, Bishop DT, Hodgson SV, Sheer D, Northover JM, Talbot IC, Solomon E, Bodmer WF (1996) Genetic mapping of hereditary mixed polyposis syndrome to chromosome 6q. Am J Hum Genet 58(4):770–776

    PubMed  CAS  Google Scholar 

  65. Farrington SM, Tenesa A, Barnetson R, Wiltshire A, Prendergast J, Porteous M, Campbell H, Dunlop MG (2005) Germline susceptibility to colorectal cancer due to base-excision repair gene defects. Am J Hum Genet 77(1):112–119

    Article  PubMed  CAS  Google Scholar 

  66. Jaeger EE, Woodford-Richens KL, Lockett M, Rowan AJ, Sawyer EJ, Heinimann K, Rozen P, Murday VA, Whitelaw SC, Ginsberg A, Atkin WS, Lynch HT, Southey MC, Debinski H, Eng C, Bodmer WF, Talbot IC, Hodgson SV, Thomas HJ, Tomlinson IP (2003) An ancestral Ashkenazi haplotype at the HMPS/CRAC1 locus on 15q13-q14 is associated with hereditary mixed polyposis syndrome. Am J Hum Genet 72(5):1261–1267

    Article  PubMed  CAS  Google Scholar 

  67. Cao X, Eu KW, Kumarasinghe MP, Li HH, Loi C, Cheah PY (2006) Mapping of hereditary mixed polyposis syndrome (HMPS) to chromosome 10q23 by genomewide high-density single nucleotide polymorphism (SNP) scan and identification of BMPR1A loss of function. J Med Genet 43(3):e13

    Article  PubMed  CAS  Google Scholar 

  68. Jeevaratnam P, Cottier DS, Browett PJ, Van De Water NS, Pokos V, Jass JR (1996) Familial giant hyperplastic polyposis predisposing to colorectal cancer: a new hereditary bowel cancer syndrome. J Pathol 179(1):20–25

    Article  PubMed  CAS  Google Scholar 

  69. Tomlinson I, Rahman N, Frayling I, Mangion J, Barfoot R, Hamoudi R, Seal S, Northover J, Thomas HJ, Neale K, Hodgson S, Talbot I, Houlston R, Stratton MR (1999) Inherited susceptibility to colorectal adenomas and carcinomas: evidence for a new predisposition gene on 15q14-q22. Gastroenterology 116(4):789–795

    Article  PubMed  CAS  Google Scholar 

  70. Takeuchi Y, Yoshikawa M, Tsukamoto N, Shiroi A, Hoshida Y, Enomoto Y, Kimura T, Yamamoto K, Shiiki H, Kikuchi E, Fukui H (2003) Cronkhite–Canada syndrome with colon cancer, portal thrombosis, high titer of antinuclear antibodies, and membranous glomerulonephritis. J Gastroenterol 38(8):791–795

    Article  PubMed  Google Scholar 

  71. Yoshida S, Tomita H (2002) A case of Cronkhite–Canada syndrome whose major complaint, taste disturbance, was improved by zinc therapy. Acta Otolaryngol Suppl 546:154–158

    Article  PubMed  Google Scholar 

  72. Blonski WC, Furth EE, Kinosian BP, Compher C, Metz DC (2005) A case of Cronkhite–Canada syndrome with taste disturbance as a leading complaint. Digestion 71(4):201–205

    Article  PubMed  Google Scholar 

  73. Egawa T, Kubota T, Otani Y, Kurihara N, Abe S, Kimata M, Tokuyama J, Wada N, Suganuma K, Kuwano Y, Kumai K, Sugino Y, Mukai M, Kitajima M (2000) Surgically treated Cronkhite–Canada syndrome associated with gastric cancer. Gastric Cancer 3(3):156–160

    Article  PubMed  Google Scholar 

  74. Yashiro M, Kobayashi H, Kubo N, Nishiguchi Y, Wakasa K, Hirakawa K (2004) Cronkhite–Canada syndrome containing colon cancer and serrated adenoma lesions. Digestion 69(1):57–62

    Article  PubMed  Google Scholar 

  75. Calva D, Howe JR (2008) Hamartomatous polyposis syndromes. Surg Clin North Am 88(4):779–817

    Article  PubMed  Google Scholar 

  76. Epstein EH (2008) Basal cell carcinomas: attack of the hedgehog. Nat Rev Cancer 8(10):743–754

    Article  PubMed  CAS  Google Scholar 

  77. Hahn H, Wicking C, Zaphiropoulous PG, Gailani MR, Shanley S, Chidambaram A, Vorechovsky I, Holmberg E, Unden AB, Gillies S, Negus K, Smyth I, Pressman C, Leffell DJ, Gerrard B, Goldstein AM, Dean M, Toftgard R, Chenevix-Trench G, Wainwright B, Bale AE (1996) Mutations of the human homolog of drosophila patched in the nevoid basal cell carcinoma syndrome. Cell 85(6):841–851

    Article  PubMed  CAS  Google Scholar 

  78. Johnson RL, Rothman AL, Xie J, Goodrich LV, Bare JW, Bonifas JM, Quinn AG, Myers RM, Cox DR, Epstein EH Jr, Scott MP (1996) Human homolog of patched, a candidate gene for the basal cell nevus syndrome. Science 272(5268):1668–1671

    Article  PubMed  CAS  Google Scholar 

  79. Gutmann DH, Aylsworth A, Carey JC, Korf B, Marks J, Pyeritz RE, Rubenstein A, Viskochil D (1997) The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. JAMA 278(1):51–57

    Article  PubMed  CAS  Google Scholar 

  80. Jacob S, Prabhakar BR, Singh SK, Mammen KJ (1998) Neurofibromatosis of the colon: an unusual manifestation of von Recklinghausen’s diseases—a case report. Indian J Pathol Microbiol 41(1):113–116

    PubMed  CAS  Google Scholar 

  81. Chan OT, Haghighi P (2006) Hamartomatous polyps of the colon: ganglioneuromatous, stromal, and lipomatous. Arch Pathol Lab Med 130(10):1561–1566

    PubMed  Google Scholar 

  82. Weiss B, Bollag G, Shannon K (1999) Hyperactive Ras as a therapeutic target in neurofibromatosis type 1. Am J Med Genet 89(1):14–22

    PubMed  CAS  Google Scholar 

  83. Kaplan J, Cushing B, Chang CH, Poland R, Roscamp J, Perrin E, Bhaya N (1982) Familial T-cell lymphoblastic lymphoma. Association with Von Recklinghausen neurofibromatosis and Gardner syndrome. Am J Hematol 12(3):247–250

    Article  PubMed  CAS  Google Scholar 

  84. Shen MH, Harper PS, Upadhyaya M (1996) Molecular genetics of neurofibromatosis type 1 (NF1). J Med Genet 33(1):2–17

    Article  PubMed  CAS  Google Scholar 

  85. Lynch HT, Fitzgibbons RJ Jr, Lanspa SJ, Marcus JN, Lynch JF, Kopelovich L (1987) Familial polyposis coli and neurofibromatosis in the same patient: a family study. Cancer Genet Cytogenet 28(2):245–251

    Article  PubMed  CAS  Google Scholar 

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  1. GI Division, Shanghai Institute of Digestive Disease, Shanghai Jiao-Tong University School of Medicine—Renji Hospital, 145 Shandong Road Middle, Shanghai, 200001, People’s Republic of China

    Hui-Min Chen & Jing-Yuan Fang

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Chen, HM., Fang, JY. Genetics of the hamartomatous polyposis syndromes: a molecular review. Int J Colorectal Dis 24, 865–874 (2009). https://doi.org/10.1007/s00384-009-0714-2

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