Latest Review of Methylation Status of Cholangiocarcinoma Related Genes in Carcinogenesis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

XUE Lixin ¹ , LI Kezhou ²

1.Department of General Surgery, Luzhou Medical College Hospital, Luzhou 646000, Sichuan Province, China;;
2.Department of Hepatobiliopancreatic Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China;

Corresponding author：

Keywords：

DNA methylation; Cholangiocarcinoma; Cholangiocarcinoma-related gene; Diagnosis and treatment

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ObjectiveRecent advancements in the researches on cholangiocarcinoma (CC) related genes methylation in CC were reviewed and the clinical significances of aberrant DNA methylation for the diagnosis and treatment of CC were discussed. MethodsRelevant literatures about the relation between CC-related genes methylation and CC published recently were collected and reviewed. ResultsThe genesis of CC resulted from abnormal expressions of many genes. Many researches had shown that the abnormal methylation of CC-related genes had a close relation with CC. Epigenetic alteration had been acknowledged as an important mechanism contributing to early CC carcinogenesis. ConclusionsAbnormal methylation of CC-related genes is related with CC. The detection of CC-related genes methylation might provide new specific biomarkers for early noninvasive diagnosis of this disease. Using epigenetic agents such as azacytidine to modulate the activities of DNA methyltransferase and reverse the methylation status of CC-related gene might be an attractive strategy for future treatment of CC, which could be combined with conventional therapies.

Citation： XUE Lixin ,LI Kezhou. Latest Review of Methylation Status of Cholangiocarcinoma Related Genes in Carcinogenesis. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2011, 18(6): 672-675. doi: Copy

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2.	Maruyama R, Toyooka S, Toyooka KO, et al. Aberrant promoter methylation profile of prostate cancers and its relationship to clinicopathological features [J]. Clin Cancer Res, 2002, 8(2): 514519.
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6.	Yang B, House MG, Guo M, et al. Promoter methylation profiles of tumor suppressor genes in intrahepatic and extrahepatic cholangiocarcinoma [J]. Mod Pathol, 2005, 18(3): 412420.
7.	Lee S, Kim WH, Jung HY, et al. Aberrant CpG island methylation of multiple genes in intrahepatic cholangiocarcinoma [J]. Am J Pathol, 2002, 161(3): 10151022.
8.	Tozawa T, Tamura G, Honda T, et al. Promoter hypermethylation of DAPkinase is associated with poor survival in primary biliary tract carcinoma patients [J]. Cancer Sci, 2004, 95(9): 736740.
9.	Isomoto H. Epigenetic alterations associated with cholangiocarcinoma (review) [J]. Oncol Rep, 2009, 22(2): 227232.
10.	Klump B, Hsieh CJ, Dette S, et al. Promoter methylation of INK4a/ARF as detected in bilesignificance for the differential diagnosis in biliary disease [J]. Clin Cancer Res, 2003, 9(5): 17731778.
11.	Koga Y, Kitajima Y, Miyoshi A, et al. Tumor progression through epigenetic gene silencing of O(6)methylguanineDNA methyltransferase in human biliary tract cancers [J]. Ann Surg Oncol, 2005, 12(5): 354363.
12.	Hong SM, Choi J, Ryu K, et al. Promoter hypermethylation of the p16 gene and loss of its protein expression is correlated with tumor progression in extrahepatic bile duct carcinomas [J]. Arch Pathol Lab Med, 2006, 130(1): 3338.
13.	Chinnasri P, Pairojkul C, Jearanaikoon P, et al. Preferentially different mechanisms of inactivation of 9p21 gene cluster in liver flukerelated cholangiocarcinoma [J]. Hum Pathol, 2009, 40(6): 817826.
14.	Kim BH, Cho NY, Shin SH, et al. CpG island hypermethylation and repetitive DNA hypomethylation in premalignant lesion of extrahepatic cholangiocarcinoma [J]. Virchows Arch, 2009, 455(4): 343351.
15.	Wong N, Li L, Tsang K, et al. Frequent loss of chromosome 3p and hypermethylation of RASSF1A in cholangiocarcinoma [J]. J Hepatol, 2002, 37(5): 633639.
16.	Liu XF, Zhu SG, Zhang H, et al. The methylation status of the TMS1/ASC gene in cholangiocarcinoma and its clinical significance [J]. Hepatobiliary Pancreat Dis Int, 2006, 5(3): 449453.
17.	Tischoff I, Markwarth A, Witzigmann H, et al. Allele loss and epigenetic inactivation of 3p21.3 in malignant liver tumors [J]. Int J Cancer, 2005, 115(5): 684689.
18.	Abraham SC, Lee JH, Boitnott JK, et al. Microsatellite instability in intraductal papillary neoplasms of the biliary tract [J]. Mod Pathol, 2002, 15(12): 13091317.
19.	Limpaiboon T, Khaenam P, Chinnasri P, et al.Promoter hypermethylation is a major event of hMLH1 gene inactivation in liver fluke related cholangiocarcinoma [J]. Cancer Lett, 2005, 217(2): 213219.
20.	Isomoto H, Mott JL, Kobayashi S, et al. Sustained IL6/STAT3 signaling in cholangiocarcinoma cells due to SOCS3 epigenetic silencing [J]. Gastroenterology, 2007, 132(1): 384396.
21.	McGinnis W, Krumlauf R. Homeobox genes and axial patterning [J]. Cell, 1992, 68(2): 283302.
22.	Roberts DJ, Smith DM, Goff DJ, et al. Epithelialmesenchymal signaling during the regionalization of the chick gut [J]. Development, 1998, 125(15): 2791801.
23.	Uchida T, Wada K, Akamatsu T, et al. A novel epidermal growth factorlike molecule containing two follistatin modules stimulates tyrosine phosphorylation of erbB4 in MKN28 gastric cancer cells [J]. Biochem Biophys Res Commun, 1999, 266(2): 593602.
24.	Young J, Biden KG, Simms LA, et al. HPP1: a transmembrane proteinencoding gene commonly methylated in colorectal polyps and cancers [J]. Proc Natl Acad Sci USA, 2001, 98(1): 265270.
25.	McCormick MB, Tamimi RM, Snider L, et al. NeuroD2 and neuroD3: distinct expression patterns and transcriptional activation potentials within the neuroD gene family [J]. Mol Cell Biol, 1996, 16(10): 57925800.
26.	Ogino S, Cantor M, Kawasaki T, et al. CpG island methylator phenotype (CIMP) of colorectal cancer is best characterised by quantitative DNA methylation analysis and prospective cohort studies [J]. Gut, 2006, 55(7): 10001006.
27.	Kim BH, Cho NY, Choi M, et al. Methylation profiles of multiple CpG island loci in extrahepatic cholangiocarcinoma versus those of intrahepatic cholangiocarcinomas [J]. Arch Pathol Lab Med, 2007, 131(6): 923930.
28.	Tannapfel A, Benicke M, Katalinic A, et al. Frequency of p16(INK4A) alterations and Kras mutations in intrahepatic cholangiocarcinoma of the liver [J]. Gut, 2000, 47(5): 721727.
29.	Chen YJ, Tang QB, Zou SQ. Inactivation of RASSF1A, the tumor suppressor gene at 3p21.3 in extrahepatic cholangiocarcinoma [J]. World J Gastroenterol, 2005, 11(9): 13331338.
30.	Hermann A, Gowher H, Jeltsch A. Biochemistry and biology of mammalian DNA methyltransferases[J]. Cell Mol Life Sci, 2004, 61(1920): 25712587.
31.	Fang JY, Yang L, Zhu HY, et al. 5Aza2’deoxycitydine induces demethylation and upregulates transcription of p16INK4A gene in human gastric cancer cell lines [J]. Chin Med J (Engl), 2004, 117(1): 99103.
32.	唐启彬, 孙华文, 邹声泉. 5氮2脱氧胞苷体内外抑制胆管癌细胞生长的研究 [J]. 中华普通外科杂志, 2004, 19(5): 295297.

1. Harder J, Blum HE.. Cholangiocarcinoma [J]. Praxis (Bern 1994), 2002, 91(34): 13521356.
2. Maruyama R, Toyooka S, Toyooka KO, et al. Aberrant promoter methylation profile of prostate cancers and its relationship to clinicopathological features [J]. Clin Cancer Res, 2002, 8(2): 514519.
3. Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer [J]. Nat Rev Genet, 2002, 3(6): 415428.
4. Balmain A, Gray J, Ponder B. The genetics and genomics of cancer [J]. Nat Genet, 2003, 33 Suppl: 238244.
5. Singal R, Ginder GD. DNA methylation [J]. Blood, 1999, 93(12): 40594070.
6. Yang B, House MG, Guo M, et al. Promoter methylation profiles of tumor suppressor genes in intrahepatic and extrahepatic cholangiocarcinoma [J]. Mod Pathol, 2005, 18(3): 412420.
7. Lee S, Kim WH, Jung HY, et al. Aberrant CpG island methylation of multiple genes in intrahepatic cholangiocarcinoma [J]. Am J Pathol, 2002, 161(3): 10151022.
8. Tozawa T, Tamura G, Honda T, et al. Promoter hypermethylation of DAPkinase is associated with poor survival in primary biliary tract carcinoma patients [J]. Cancer Sci, 2004, 95(9): 736740.
9. Isomoto H. Epigenetic alterations associated with cholangiocarcinoma (review) [J]. Oncol Rep, 2009, 22(2): 227232.
10. Klump B, Hsieh CJ, Dette S, et al. Promoter methylation of INK4a/ARF as detected in bilesignificance for the differential diagnosis in biliary disease [J]. Clin Cancer Res, 2003, 9(5): 17731778.
11. Koga Y, Kitajima Y, Miyoshi A, et al. Tumor progression through epigenetic gene silencing of O(6)methylguanineDNA methyltransferase in human biliary tract cancers [J]. Ann Surg Oncol, 2005, 12(5): 354363.
12. Hong SM, Choi J, Ryu K, et al. Promoter hypermethylation of the p16 gene and loss of its protein expression is correlated with tumor progression in extrahepatic bile duct carcinomas [J]. Arch Pathol Lab Med, 2006, 130(1): 3338.
13. Chinnasri P, Pairojkul C, Jearanaikoon P, et al. Preferentially different mechanisms of inactivation of 9p21 gene cluster in liver flukerelated cholangiocarcinoma [J]. Hum Pathol, 2009, 40(6): 817826.
14. Kim BH, Cho NY, Shin SH, et al. CpG island hypermethylation and repetitive DNA hypomethylation in premalignant lesion of extrahepatic cholangiocarcinoma [J]. Virchows Arch, 2009, 455(4): 343351.
15. Wong N, Li L, Tsang K, et al. Frequent loss of chromosome 3p and hypermethylation of RASSF1A in cholangiocarcinoma [J]. J Hepatol, 2002, 37(5): 633639.
16. Liu XF, Zhu SG, Zhang H, et al. The methylation status of the TMS1/ASC gene in cholangiocarcinoma and its clinical significance [J]. Hepatobiliary Pancreat Dis Int, 2006, 5(3): 449453.
17. Tischoff I, Markwarth A, Witzigmann H, et al. Allele loss and epigenetic inactivation of 3p21.3 in malignant liver tumors [J]. Int J Cancer, 2005, 115(5): 684689.
18. Abraham SC, Lee JH, Boitnott JK, et al. Microsatellite instability in intraductal papillary neoplasms of the biliary tract [J]. Mod Pathol, 2002, 15(12): 13091317.
19. Limpaiboon T, Khaenam P, Chinnasri P, et al.Promoter hypermethylation is a major event of hMLH1 gene inactivation in liver fluke related cholangiocarcinoma [J]. Cancer Lett, 2005, 217(2): 213219.
20. Isomoto H, Mott JL, Kobayashi S, et al. Sustained IL6/STAT3 signaling in cholangiocarcinoma cells due to SOCS3 epigenetic silencing [J]. Gastroenterology, 2007, 132(1): 384396.
21. McGinnis W, Krumlauf R. Homeobox genes and axial patterning [J]. Cell, 1992, 68(2): 283302.
22. Roberts DJ, Smith DM, Goff DJ, et al. Epithelialmesenchymal signaling during the regionalization of the chick gut [J]. Development, 1998, 125(15): 2791801.
23. Uchida T, Wada K, Akamatsu T, et al. A novel epidermal growth factorlike molecule containing two follistatin modules stimulates tyrosine phosphorylation of erbB4 in MKN28 gastric cancer cells [J]. Biochem Biophys Res Commun, 1999, 266(2): 593602.
24. Young J, Biden KG, Simms LA, et al. HPP1: a transmembrane proteinencoding gene commonly methylated in colorectal polyps and cancers [J]. Proc Natl Acad Sci USA, 2001, 98(1): 265270.
25. McCormick MB, Tamimi RM, Snider L, et al. NeuroD2 and neuroD3: distinct expression patterns and transcriptional activation potentials within the neuroD gene family [J]. Mol Cell Biol, 1996, 16(10): 57925800.
26. Ogino S, Cantor M, Kawasaki T, et al. CpG island methylator phenotype (CIMP) of colorectal cancer is best characterised by quantitative DNA methylation analysis and prospective cohort studies [J]. Gut, 2006, 55(7): 10001006.
27. Kim BH, Cho NY, Choi M, et al. Methylation profiles of multiple CpG island loci in extrahepatic cholangiocarcinoma versus those of intrahepatic cholangiocarcinomas [J]. Arch Pathol Lab Med, 2007, 131(6): 923930.
28. Tannapfel A, Benicke M, Katalinic A, et al. Frequency of p16(INK4A) alterations and Kras mutations in intrahepatic cholangiocarcinoma of the liver [J]. Gut, 2000, 47(5): 721727.
29. Chen YJ, Tang QB, Zou SQ. Inactivation of RASSF1A, the tumor suppressor gene at 3p21.3 in extrahepatic cholangiocarcinoma [J]. World J Gastroenterol, 2005, 11(9): 13331338.
30. Hermann A, Gowher H, Jeltsch A. Biochemistry and biology of mammalian DNA methyltransferases[J]. Cell Mol Life Sci, 2004, 61(1920): 25712587.
31. Fang JY, Yang L, Zhu HY, et al. 5Aza2’deoxycitydine induces demethylation and upregulates transcription of p16INK4A gene in human gastric cancer cell lines [J]. Chin Med J (Engl), 2004, 117(1): 99103.
32. 唐启彬, 孙华文, 邹声泉. 5氮2脱氧胞苷体内外抑制胆管癌细胞生长的研究 [J]. 中华普通外科杂志, 2004, 19(5): 295297.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Latest Review of Methylation Status of Cholangiocarcinoma Related Genes in Carcinogenesis

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