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目的 探讨胆管癌的表遗传学改变。方法 用甲基化特异PCR(MSP)法 ,检测了 12个候选肿瘤抑制基因 (APGE cad herin/CDH1,MGMT ,RASSF1A ,GSTP ,RAR β ,p14 ARF,p15 INK4b,p16INK4a,p73 ,hMLH1,DAPK)启动子在 72例胆管癌中的甲基化情况 ,其中肝内和肝外胆管癌各 3 6例 ,10例良性胆管上皮作为对照。结果 85 %的胆管癌至少有一个肿瘤抑制基因的甲基化 ,在胆管癌中 ,肿瘤抑制基因的甲基化顺序是 :RASSF1A(65 %) ,p15 INK4b(5 0 %) ,p16INK4a(5 0 %) ,APC(4 6%) ,E cadherin/CDH1(4 3 %) ,p14 ARF(3 8%) ,p73 (3 6%) ,MGMT(3 3 %) ,hMHL1(2 5 %) ,GSTP(14 %) ,RAR β(14 %)和DAPK(3 %)。虽然单个肿瘤抑制基因的甲基化可见于良性胆管上皮 ,但是多个肿瘤抑制基因的甲基化只见于胆管癌。约 70 %(5 0 /72 )的胆管癌有 3个或 3个以上的肿瘤抑制基因的甲基化 ,5 2 %(3 8/72 )有 4个或 4个以上肿瘤抑制基因的甲基化。多个肿瘤抑制基因的协同甲基化 ,和RASSF1A ,p15 INK4b,p16INK4a和 /或hMHL1密切相关。RASSF1A的甲基化在肝外胆管癌 (83 %)较肝内胆管癌更常见 (4 7%) (P =0 . 0 0 3 ) ,而GSTP更多见于肝内胆管癌(肝内 3 1%,肝外 6%,P =0 . 0 12 ) ,本研究提示肿瘤抑制基因启动子CpG岛的甲基化在胆管癌中是一?
Objective To investigate the epigenetic changes of cholangiocarcinoma. Methods 12 candidate tumor suppressor genes (APGE cad herin / CDH1, MGMT, RASSF1A, GSTP, RAR β, p14 ARF, p15 INK4b, p16INK4a, p73, hMLH1 and DAPK) were detected by methylation specific PCR (MSP) Promoter methylation in 72 cases of cholangiocarcinoma, including 36 cases of intrahepatic and extrahepatic cholangiocarcinoma, 10 cases of benign biliary epithelium as a control. Results Methylation of at least one tumor suppressor gene was found in 85% of cholangiocarcinomas. The methylation of tumor suppressor genes in cholangiocarcinoma was RASSF1A (65%), p15 INK4b (50%), p16INK4a (38%), APC (43%), E cadherin / CDH1 (43%), p14 ARF (38%), p73 (36%), MGMT (33%), hMHL1 (14%), RAR β (14%) and DAPK (3%). Although methylation of a single tumor suppressor gene is found in benign biliary epithelium, methylation of multiple tumor suppressor genes is found only in cholangiocarcinomas. Approximately 70% (50/72) of cholangiocarcinomas have methylation of 3 or more tumor suppressor genes, 52 (38%) have 4 or more of the tumor suppressor genes of methyl The Co-methylation of multiple tumor suppressor genes is closely related to RASSF1A, p15 INK4b, p16INK4a and / or hMHL1. Methylation of RASSF1A was more common in extrahepatic cholangiocarcinoma (83%) than intrahepatic cholangiocarcinoma (47%) (P = 0.003), whereas GSTP was found more commonly in intrahepatic cholangiocarcinoma %, Extrahepatic 6%, P = .012), this study suggests that CpG island methylation of the tumor suppressor gene promoter is one in cholangiocarcinoma?