Skip to main content
SpringerLink
Log in

Role of epigenetic alterations in cholangiocarcinoma

  • Published:
Journal of Hepato-Biliary-Pancreatic Surgery

Abstract

Intrahepatic cholangiocarcinomas are rare malignant epithelial liver tumors arising from intrahepatic bile ducts. The prognosis of affected patients is poor. Several risk factors, including hepatolithiasis, liver fluke infection, and anatomical abnormalities associated with inflammation of the biliary tract have been described. At present, little is known about the cellular and molecular mechanisms leading to the development of cholangiocarcinoma. In recent years, in addition to genetic alterations, epigenetic inactivation of (tumor suppressor) genes by promoter CpG island hypermethylation has been recognized as an important and alternative mechanism in tumorigenesis. This review discusses the epi-genetic inactivation of different tumor suppressor genes in cholangiocarcinoma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Ch Wittekind (1995) Hepatocellular carcinoma and cholangiocarcinoma P Hermanek MK Gospodarowicz DE Henson (Eds) Prognostic factors in cancer Springer Berlin Heidelberg New York Tokyo 88–93

    Google Scholar 

  2. J Harder HE Blum (2002) ArticleTitleCholangiocarcinoma Schweiz Med Rundsch Prax 91 1352–6 Occurrence Handle1:STN:280:DC%2BD38vnt1SisA%3D%3D

    CAS  Google Scholar 

  3. P Watanapa (1996) ArticleTitleCholangiocarcinoma in patients with opisthorchiasis Br J Surg 83 1062–4 Occurrence Handle8869303 Occurrence Handle1:STN:280:ByiD383psVc%3D

    PubMed  CAS  Google Scholar 

  4. HR Shin CU Lee HJ Park SY Seol JM Chung HC Choi et al. (1996) ArticleTitleHepatitis B and C virus, Clonorchensis sinensis for risk of liver cancer: a case-control study in Pusan, Korea Int J Epidemiol 25 933–40 Occurrence Handle8921477 Occurrence Handle1:STN:280:ByiD2sbns1I%3D

    PubMed  CAS  Google Scholar 

  5. P Watanapa WB Watanapa (2002) ArticleTitleLiver fluke-associated cholangiocarcinoma Br J Surg 89 962–70 Occurrence Handle12153620 Occurrence Handle1:STN:280:DC%2BD38vgsVeitg%3D%3D Occurrence Handle10.1046/j.1365-2168.2002.02143.x

    Article  PubMed  CAS  Google Scholar 

  6. S Kubo H Kinoshita K Hirohashi H Hamba (1995) ArticleTitleHepatolithiasis associated with cholangiocarcinoma World J Surg 19 637–41 Occurrence Handle7676713 Occurrence Handle1:STN:280:ByqH3cjhvVc%3D Occurrence Handle10.1007/BF00294744

    Article  PubMed  CAS  Google Scholar 

  7. PA Lipsett HA Pitt PM Colombani JK Boitnott JL Cameron (1994) ArticleTitleCholedochal cyst disease. A changing pattern of presentation Ann Surg 220 644–52 Occurrence Handle7979612 Occurrence Handle1:STN:280:ByqD2s%2FjvVw%3D

    PubMed  CAS  Google Scholar 

  8. YK Kang WH Kim HW Lee HK Lee Y Kim (1999) ArticleTitleMutation of p53 and k-ras and loss of heterozygosity of APC in intrahepatic cholangiocarcinoma Lab Invest 79 477–83 Occurrence Handle10212000 Occurrence Handle1:CAS:528:DyaK1MXivVGku7g%3D

    PubMed  CAS  Google Scholar 

  9. S Yoshida T Todoroki Y Ichikawa S Hanai H Suzuki M Hori et al. (1995) ArticleTitleMutations of p16Ink4A/CDKN2 and p15Ink4B/MTS2 genes in biliary tract cancers Cancer Res 55 2756–60 Occurrence Handle7796400 Occurrence Handle1:CAS:528:DyaK2MXmsFyksrk%3D

    PubMed  CAS  Google Scholar 

  10. SA Hahn D Bartsch A Schroers H Galehdari M Becker A Ramaswamy et al. (1998) ArticleTitleMutations of the DPC4/Smad4 gene in biliary tract carcinoma Cancer Res 58 1124–6 Occurrence Handle9515793 Occurrence Handle1:CAS:528:DyaK1cXhvV2ku7c%3D

    PubMed  CAS  Google Scholar 

  11. K Shiraishi K Okita N Kusano T Harada S Kondoh S Okita et al. (2001) ArticleTitleA comparison of DNA copy number changes detected by comparative genomic hybridization in malignancies of the liver, biliary tract and pancreas Oncology 60 151–61 Occurrence Handle11244331 Occurrence Handle1:CAS:528:DC%2BD3MXit1ekt7g%3D Occurrence Handle10.1159/000055313

    Article  PubMed  CAS  Google Scholar 

  12. J Kawaki M Miyazaki H Iro K Nakagawa H Shimizu H Yoshidome et al. (2000) ArticleTitleAllelic loss in human intrahepatic cholangiocarcinoma: correlation between chromosome 8p22 and tumor progression Int J Cancer 88 228–31 Occurrence Handle11004673 Occurrence Handle1:CAS:528:DC%2BD3cXntlynurw%3D Occurrence Handle10.1002/1097-0215(20001015)88:2<228::AID-IJC13>3.0.CO;2-8

    Article  PubMed  CAS  Google Scholar 

  13. SB Baylin JG Herman (2000) ArticleTitleDNA hypermethylation in tumorigenesis: epigenetic joins genetic Trends Genet 16 168–74 Occurrence Handle10729832 Occurrence Handle1:CAS:528:DC%2BD3cXit1Sqsbg%3D Occurrence Handle10.1016/S0168-9525(99)01971-X

    Article  PubMed  CAS  Google Scholar 

  14. M Okano DW Bell DA Haber E Li (1999) ArticleTitleDNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development Cell 99 247–57 Occurrence Handle10555141 Occurrence Handle1:CAS:528:DyaK1MXnt1Gqsrc%3D Occurrence Handle10.1016/S0092-8674(00)81656-6

    Article  PubMed  CAS  Google Scholar 

  15. AD Riggs GP Pfeifer (1992) ArticleTitleX-chromosome in activation and cell memory Trends Genet 8 169–74 Occurrence Handle1369742 Occurrence Handle1:STN:280:ByqA3svosVY%3D

    PubMed  CAS  Google Scholar 

  16. A Razin H Cedar (1994) ArticleTitleDNA methylation and genomic imprinting Cell 77 473–6 Occurrence Handle8187170 Occurrence Handle1:CAS:528:DyaK2cXltVSks78%3D Occurrence Handle10.1016/0092-8674(94)90208-9

    Article  PubMed  CAS  Google Scholar 

  17. AP Feinberg B Vogelstein (1983) ArticleTitleHypomethylation distinguishes genes of some human cancers from their normal counterparts Nature 301 89–92 Occurrence Handle6185846 Occurrence Handle1:CAS:528:DyaL3sXms1ertA%3D%3D Occurrence Handle10.1038/301089a0

    Article  PubMed  CAS  Google Scholar 

  18. AP Feinberg (2001) Genomic imprinting and cancer CR Scriver AL Beaudet WS Sly D Valle (Eds) The metabolic and molecular bases of inherited disease McGraw-Hill New York 525–37

    Google Scholar 

  19. M Esteller PG Corn SB Baylin JG Herman (2001) ArticleTitleA gene hypermethylation profile of human cancer Cancer Res 61 3225–9 Occurrence Handle11309270 Occurrence Handle1:CAS:528:DC%2BD3MXjtFSjt7g%3D

    PubMed  CAS  Google Scholar 

  20. A Tannapfel L Weinans F Geissler A Schütz A Katalinic F Kockerling et al. (2000) ArticleTitleMutations of p53 tumor suppressor gene, apoptosis and proliferation in intrahepatic cholangiocarcinoma of the liver Dig Dis Sci 45 317–24 Occurrence Handle10711445 Occurrence Handle1:CAS:528:DC%2BD3cXitVCgt74%3D Occurrence Handle10.1023/A:1005412626515

    Article  PubMed  CAS  Google Scholar 

  21. WH Liggett SuffixJr D Sidransky (1998) ArticleTitleRole of the P16 tumor suppressor gene in cancer J Clin Oncol 16 1197–206 Occurrence Handle9508208 Occurrence Handle1:CAS:528:DyaK1cXitVKitb8%3D

    PubMed  CAS  Google Scholar 

  22. A Tannapfel F Sommerer M Benicke L Weinans A Katalinic F GeiMßler et al. (2002) ArticleTitleGenetic and epigenetic alterations of the INK4a-ARF pathway in cholangiocarcinoma J Pathol 197 624–31 Occurrence Handle12210082 Occurrence Handle1:CAS:528:DC%2BD38Xntleku78%3D Occurrence Handle10.1002/path.1139

    Article  PubMed  CAS  Google Scholar 

  23. B Yang MG House G Mingzhou JG Herman DP Clark (2005) ArticleTitlePromoter methylation profiles of tumor suppressor genes in intrahepatic and extrahepatic cholangiocarcinoma Mod Pathol 18 412–20 Occurrence Handle15467712 Occurrence Handle1:CAS:528:DC%2BD2MXhtlertbc%3D Occurrence Handle10.1038/modpathol.3800287

    Article  PubMed  CAS  Google Scholar 

  24. A Tannapfel M Benicke A Katalinic D Uhlmann F Köckerling J Hauss et al. (2000) ArticleTitleFrequency of p16INK4A alterations and k-ras mutations in intrahepatic cholangiocarcinoma of the liver Gut 47 721–7 Occurrence Handle11034592 Occurrence Handle1:CAS:528:DC%2BD3cXosVSgurg%3D Occurrence Handle10.1136/gut.47.5.721

    Article  PubMed  CAS  Google Scholar 

  25. A Ishikawa M Sasaki Y Sato Ohira Sh MF Chen SF Huang et al. (2004) ArticleTitleFrequent p16ink4a inactivation is an early and frequent event of intraductal papillary neoplasm of the liver arising in hepatolithiasis Hum Pathol 35 1505–14 Occurrence Handle15619210 Occurrence Handle1:CAS:528:DC%2BD2cXhtVyku77E Occurrence Handle10.1016/j.humpath.2004.08.014

    Article  PubMed  CAS  Google Scholar 

  26. T Raveh A Kimchi (2001) ArticleTitleDAP kinase — a proapoptotic gene that functions As a tumor suppressor Exp Cell Res 264 185–92 Occurrence Handle11237533 Occurrence Handle1:CAS:528:DC%2BD3MXhsFOhur8%3D Occurrence Handle10.1006/excr.2000.5134

    Article  PubMed  CAS  Google Scholar 

  27. Y Koga Y Kitajima A Miyoshi K Sato K Kitahara H Soejima et al. (2005) ArticleTitleTumor progression through epigenetic gene silencing of O6-methylguanine-DNA methyltransferase in human biliary tract cancers Ann Surg Oncol 12 1–10 Occurrence Handle10.1245/ASO.2005.07.020

    Article  Google Scholar 

  28. CL Sommers EW Thompson JA Torri R Kemler EP Gelmann SW Byers (1991) ArticleTitleCell adhesion molecule uvomorulin expression in human breast cancer cell lines: relationship to morphology and invasive capacities Cell Growth Differ 2 365–72 Occurrence Handle1793731 Occurrence Handle1:CAS:528:DyaK38Xht1Grtro%3D

    PubMed  CAS  Google Scholar 

  29. H Oka H Shiozaki K Kobayashi M Inoue H Tahara T Kobayashi et al. (1993) ArticleTitleExpression of E-cadherin cell adhesion molecules in human breast cancer tissue and its relationship to metastasis Cancer Res 53 1696–701 Occurrence Handle8453644 Occurrence Handle1:CAS:528:DyaK3sXitlWgu7o%3D

    PubMed  CAS  Google Scholar 

  30. K Endo K Ashida N Miyake T Terada (2001) ArticleTitleE-cadherin gene mutations in human intrahepatic cholangiocarcinoma J Pathol 193 310–17 Occurrence Handle11241409 Occurrence Handle1:CAS:528:DC%2BD3MXisFynsLk%3D Occurrence Handle10.1002/1096-9896(2000)9999:9999<::AID-PATH816>3.0.CO;2-K

    Article  PubMed  CAS  Google Scholar 

  31. S Lee WH Kim HY Jung MH Yang Kang GH. Aberrant (2002) ArticleTitleCpG island methylation of multiple genes in intrahepatic cholangiocarcinoma Am J Pathol 161 1015–22 Occurrence Handle12213730 Occurrence Handle1:CAS:528:DC%2BD38XnsFOis74%3D

    PubMed  CAS  Google Scholar 

  32. H Kim J Jen B Vogelstein SR Hamilton (1994) ArticleTitleClinical and pathological characteristics of sporadic carcinomas with microsatellite sequences Am J Pathol 145 148–56 Occurrence Handle8030745 Occurrence Handle1:CAS:528:DyaK2cXlsFCns78%3D

    PubMed  CAS  Google Scholar 

  33. C Oliveria R Seruca M Sexias M Sobrinho-Simoes (1998) ArticleTitleThe clinicopathological features of gastric carcinomas with microsatellite instability may be mediated by mutations of different genes; a study of the TGFβ, IGF2R, and the BAX genes Am J Pathol 153 1211–19

    Google Scholar 

  34. D Liu H Momoi L Li Y Ishikawa M Fukumoto (2002) ArticleTitleMicrosatellite instability in Thorotrast-induced human intrahepatic cholangiocarcinoma Int J Cancer 102 366–71 Occurrence Handle12402306 Occurrence Handle1:CAS:528:DC%2BD38Xos1ajtLY%3D Occurrence Handle10.1002/ijc.10726

    Article  PubMed  CAS  Google Scholar 

  35. T Limpaiboon P Khaenam P Chinnasri M Soonklang P Jearanaikoon B Sripa et al. (2005) ArticleTitlePromoter hypermethylation is a major event of hMLH1 gene inactivation in liver fluke related cholangiocarcinoma Cancer Lett 217 213–9 Occurrence Handle15617839 Occurrence Handle1:CAS:528:DC%2BD2cXhtFGhtr7P Occurrence Handle10.1016/j.canlet.2004.06.020

    Article  PubMed  CAS  Google Scholar 

  36. SC Abraham JH Lee JK Boitnott P Agani EE Furth TT Wu (2002) ArticleTitleMicrosatellite instability in intraductal papillary neoplasmas of the biliary tract Mod Pathol 12 1309–17 Occurrence Handle10.1097/01.MP.0000038461.80167.34

    Article  Google Scholar 

  37. M Sanchez-Cespedes M Esteller L Wu H Nawroz-Danish GH Yoo WM Koch et al. (2000) ArticleTitleGene promoter hypermethylation in tumors and serum of head and neck cancer patients Cancer Res 60 829–5

    Google Scholar 

  38. M Esteller SR Hamilton PC Burger SB Baylin JG Herman (1999) ArticleTitleInactivation of the DNA repair gene O6-mehthylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasma Cancer Res 59 793–7 Occurrence Handle10029064 Occurrence Handle1:CAS:528:DyaK1MXht1Sjurk%3D

    PubMed  CAS  Google Scholar 

  39. JD Brooks M Weinstein X Lin Y Sun SS Pin GS Bova (1998) ArticleTitleCG island methylation changes near the GSTP1 gene in prostatic intraepithelial neoplasia Cancer Epidemiol Biomarkers Prev 7 531–6 Occurrence Handle9641498 Occurrence Handle1:CAS:528:DyaK1cXktVWht74%3D

    PubMed  CAS  Google Scholar 

  40. M Esteller PG Corn JP Urena E Gabrielson SB Baylin JG Herman (1998) ArticleTitleInactivation of gluthatione-S-transferase P1 gene promoter hypermethylation in human neoplasia Cancer Res 58 4515–18 Occurrence Handle9788592 Occurrence Handle1:CAS:528:DyaK1cXmslWrsr0%3D

    PubMed  CAS  Google Scholar 

  41. JC Tchou X Lin D Freije WB Isaacs JD Brooks A Rashid et al. (2000) ArticleTitleGSTP-1 CpG island DNA hypermethylation in hepatocellular carcinomas Int J Oncol 16 663–76 Occurrence Handle10717233 Occurrence Handle1:CAS:528:DC%2BD3cXisFSlsrg%3D

    PubMed  CAS  Google Scholar 

  42. K Shiraishi K Okita N Kusano T Harada S Kondoh S Okita et al. (2001) ArticleTitleA comparison of DNA copy number changes detected by comparative genomic hybridization in malignancies of the liver, biliary tract and pancreas Oncology 60 151–61 Occurrence Handle11244331 Occurrence Handle1:CAS:528:DC%2BD3MXit1ekt7g%3D Occurrence Handle10.1159/000055313

    Article  PubMed  CAS  Google Scholar 

  43. N Wong L Li K Tsang PBS Lai KF To PJ Johnson (2002) ArticleTitleFrequent loss of chromosome 3p and hypermethylation of RASSF1A in cholangiocarcinoma J Hepatol 37 633–9 Occurrence Handle12399230 Occurrence Handle1:CAS:528:DC%2BD38XotVKktLw%3D Occurrence Handle10.1016/S0168-8278(02)00269-6

    Article  PubMed  CAS  Google Scholar 

  44. R Damman C Li JH Yoon PL Chin S Bates GP Pfeifer (2000) ArticleTitleEpigenetic inactivation of a Ras association domain family protein from the lung tumor suppressor locus 3p21.3 Nat Genet 25 315–9 Occurrence Handle10.1038/77083

    Article  Google Scholar 

  45. L Liu S Tommasi DH Lee R Dammann GP Pfeifer (2003) ArticleTitleControl of microtubule stability by the RASSF1A tumor suppressor Oncogene 22 8125–36 Occurrence Handle14603253 Occurrence Handle1:CAS:528:DC%2BD3sXoslSisLo%3D Occurrence Handle10.1038/sj.onc.1206984

    Article  PubMed  CAS  Google Scholar 

  46. L Shivakumar J Minna T Sakamaki R Pestell MA White (2002) ArticleTitleThe RASSF1A tumor suppressor blocks cell cylce progression and inhibits cyclin D1 accumulation Mol Cell Biol 22 4309–18 Occurrence Handle12024041 Occurrence Handle1:CAS:528:DC%2BD38XktlSlsrw%3D Occurrence Handle10.1128/MCB.22.12.4309-4318.2002

    Article  PubMed  CAS  Google Scholar 

  47. MS Song SJ Song NG Ayad JS Chang JH Lee HK Homg et al. (2004) ArticleTitleThe tumour suppressor RASSF1A regulates mitosis by inhibiting the APC-Cdc20 complex Nat Cell Biol 6 129–37 Occurrence Handle14743218 Occurrence Handle1:CAS:528:DC%2BD2cXosFShsA%3D%3D Occurrence Handle10.1038/ncb1091

    Article  PubMed  CAS  Google Scholar 

  48. K Dreijerink E Braga I Kuzmin L Geil FM Duh D Angeloni et al. (2001) ArticleTitleThe candidate tumor suppressor gene, RASSF1A, from human chromosome 3p21.3 is involved in kidney tumorigenesis Proc Natl Acad Sci USA 98 3563–7 Occurrence Handle10.1073/pnas.131216298

    Article  Google Scholar 

  49. I Tischoff A Markwarth H Witzigmann D Uhlmann J Hauss A Mirmohammadsadegh et al. (2005) ArticleTitleAllele loss and epigenetic inactivation of 3p21.3 in malignant liver tumors Int J Cancer 115 684–9 Occurrence Handle15704097 Occurrence Handle1:CAS:528:DC%2BD2MXkvF2ksrc%3D Occurrence Handle10.1002/ijc.20944

    Article  PubMed  CAS  Google Scholar 

  50. GH Qui LK Tan KS Loh CY Lim G Srivastava ST Tsai et al. (2004) ArticleTitleThe candidate tumor suppressor gene BLU, located at the commonly deleted region 3p21.3, is an E2F-regulated, stress reponsive gene and inactivated by both epigenetic and genetic mechanisms in nasopharyngeal carcinoma Oncogene 23 4793–806 Occurrence Handle10.1038/sj.onc.1207632

    Article  Google Scholar 

  51. A Agathanggelou A Dallol S Zöchbauer-Müller C Morrissey S Honorio L Hesson et al. (2003) ArticleTitleEpigenetic inactivation of the candidate 3p21.3 suppressor gene BLU in human cancers Oncogene 22 1580–8 Occurrence Handle12629521 Occurrence Handle1:CAS:528:DC%2BD3sXhvFShur8%3D Occurrence Handle10.1038/sj.onc.1206243

    Article  PubMed  CAS  Google Scholar 

  52. L Hesson I Bièche D Krex E Criniere K Hoang-Xuan ER Maher et al. (2004) ArticleTitleFrequent epigenetic inactivation of RASSF1A and BLU genes located within the critical 3p21.3 region in gliomas Oncogene 23 2408–19 Occurrence Handle14743209 Occurrence Handle1:CAS:528:DC%2BD2cXisVGksbw%3D Occurrence Handle10.1038/sj.onc.1207407

    Article  PubMed  CAS  Google Scholar 

  53. XQ Liu HK Chen XS Zhang ZG Pan A Li QS Feng et al. (2003) ArticleTitleAlterations of BLU, a candidate tumor suppressor gene on chromosome 3p21.3, in human nasopharyngeal carcinoma Int J Cancer 106 60–5 Occurrence Handle12794757 Occurrence Handle1:CAS:528:DC%2BD3sXltFent7c%3D Occurrence Handle10.1002/ijc.11166

    Article  PubMed  CAS  Google Scholar 

  54. T Kuroki F Trapasso S Yendamuri A Matsuyama H Alder NN Williams et al. (2003) ArticleTitleAllelic loss on chromosome 3p21.3 and promoter hypermethylation of Semaphorin 3B in non-small cell lung cancer Cancer Res 63 3352–5 Occurrence Handle12810670 Occurrence Handle1:CAS:528:DC%2BD3sXks1ehsrk%3D

    PubMed  CAS  Google Scholar 

  55. Y Tomizawa Y Sekido M Kondo B Gao J Yokota J Roche et al. (2001) ArticleTitleInhibition of lung cancer cell growth and induction of apoptosis after reexpression of 3p21.3 candidate tumor suppressor gene SEMA3B Proc Natl Acad Sci USA 98 13 954–9 Occurrence Handle1:CAS:528:DC%2BD3MXovVynur0%3D Occurrence Handle10.1073/pnas.231490898

    Article  CAS  Google Scholar 

  56. E Castro-Rivera S Ran P Thorpe JD Minna (2004) ArticleTitleSemaphorin 3B (SEMA3B) induces apoptosis in lung and breast cancer, whereas VEGF165 antagonizes this effect Proc Natl Acad Sci USA 101 11 432–7 Occurrence Handle1:CAS:528:DC%2BD2cXmvVKgurw%3D Occurrence Handle10.1073/pnas.0403969101

    Article  CAS  Google Scholar 

  57. AK Virmani A Rathi S Zöchbauer-Müller N Sacchi Y Fukuyama D Bryant et al. (2000) ArticleTitlePromoter methylation and silencing of the retinoic acid receptor-beta in lung cancer J Natl Cancer Inst 16 1303–7 Occurrence Handle10.1093/jnci/92.16.1303

    Article  Google Scholar 

  58. M Widschwendter J Berger M Hermann H Müller A Amberger M Zeschnigk et al. (2000) ArticleTitleMethylation and silencing of the retinoic acid receptor-b2 gene in breast cancer J Natl Cancer Inst 10 826–32 Occurrence Handle10.1093/jnci/92.10.826

    Article  Google Scholar 

  59. C Liu J Wang QJ Ou (2002) ArticleTitlePossible stem cell origin of human cholangiocarcinoma World J Gastroenterol 2 10–19

    Google Scholar 

  60. CB Rosen DM Nagorney RH Wiesner RJ Coffey SuffixJr NF LaRusso (1991) ArticleTitleCholangiocarcinoma complicating primary sclerosing cholangitis Ann Surg 213 21–5 Occurrence Handle1845927 Occurrence Handle1:STN:280:By6D1M%2FkslU%3D

    PubMed  CAS  Google Scholar 

  61. T Tozawa G Tamura T Honda SH Nawata W Kimura N Makino et al. (2004) ArticleTitlePromoter hypermethylation of DAP-kinase is associated with poor survival of primary biliary tract carcinoma patients Cancer Sci 95 736–40 Occurrence Handle15471559 Occurrence Handle1:CAS:528:DC%2BD2cXpvFOgurc%3D Occurrence Handle10.1111/j.1349-7006.2004.tb03254.x

    Article  PubMed  CAS  Google Scholar 

  62. YJ Chen QB Tang SQ Zou (2005) ArticleTitleInactivation of RASSF1A, the tumor suppressor gene at 3p21.3 in extrahepatic cholangiocarcinoma World J Gastroenterol 11 1333–8 Occurrence Handle15761971 Occurrence Handle1:CAS:528:DC%2BD2MXjt1yqsLc%3D

    PubMed  CAS  Google Scholar 

  63. K Caca J Feisthammel K Klee A Tannapfel H Witzigmann CH Wittekind et al. (2002) ArticleTitleInactivation of the INK4A/ARF locus and p53 in sporadic extrahepatic bile duct cancers and bile tract cancer cell lines Int J Cancer 97 481–8 Occurrence Handle11802210 Occurrence Handle1:CAS:528:DC%2BD38XkvFegtA%3D%3D Occurrence Handle10.1002/ijc.1639

    Article  PubMed  CAS  Google Scholar 

  64. SA Ahrendt CF Eisenberger L Yip A Rashid JT Chow HA Pitt et al. (1999) ArticleTitleChromosome 9p21 loss and p16 inactivation in primary sclerosing cholangitis-associated cholangiocarcinoma J Surg Res 84 88–93 Occurrence Handle10334895 Occurrence Handle1:CAS:528:DyaK1MXjtFKhtrk%3D Occurrence Handle10.1006/jsre.1999.5615

    Article  PubMed  CAS  Google Scholar 

  65. M Taniai H Higuchi LJ Burgart GJ Gores (2002) ArticleTitlep16INK4a promoter mutations are frequent in primary sclerosing cholangitis (PSC) and PSC-associated cholangiocarcinoma J Gastroenterol 123 1090–8 Occurrence Handle1:CAS:528:DC%2BD38Xotl2gu78%3D Occurrence Handle10.1053/gast.2002.36021

    Article  CAS  Google Scholar 

  66. JP Issa N Ahuja M Toyota MP Bronner TA Brentnall (2001) ArticleTitleAccelerated age-ralated CpG island methylation in ulcerative colitis Cancer Res 61 3573–7 Occurrence Handle11325821 Occurrence Handle1:CAS:528:DC%2BD3MXjsFCgtLw%3D

    PubMed  CAS  Google Scholar 

  67. TJ Jang DI Kim YM Shin HK Chang CH Yang (2001) ArticleTitlep16 (INK4a) promoter hypermethylation of non-tumorous tissue adjacent to gastric cancer is correlated with glandular atrophy and chronic inflammation Int J Cancer 93 629–34 Occurrence Handle11477571 Occurrence Handle1:CAS:528:DC%2BD3MXls1Wgtr4%3D Occurrence Handle10.1002/ijc.1394

    Article  PubMed  CAS  Google Scholar 

  68. Klump B, Hsieh CJ, Dette S, Holzmann KH, Sinn U, Ortner M, et al. Promoter methylation of INK4a/ARF as detected in bile — significance for the differential diagnosis in biliary disease. Clin Cancer Res 2003;1773–8

Download references

Author information

Authors and Affiliations

  1. Institute of Pathology, University of Leipzig, D-04103, Leipzig, Germany

    Iris Tischoff, Christian Wittekind & Andrea Tannapfel

Authors
  1. Iris Tischoff
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christian Wittekind
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andrea Tannapfel
    View author publications

    You can also search for this author in PubMed Google Scholar

About this article

Cite this article

Tischoff, I., Wittekind, C. & Tannapfel, A. Role of epigenetic alterations in cholangiocarcinoma. J Hepatobiliary Pancreat Surg 13, 274–279 (2006). https://doi.org/10.1007/s00534-005-1055-3

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00534-005-1055-3

Key words

Search

Navigation