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Epigenetic instability is rare in fibrolamellar carcinomas but common in viral-associated hepatocellular carcinomas

机译:表观遗传不稳定性在纤维状薄层癌中很少见,但在病毒相关肝细胞癌中很常见

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Fibrolamellar carcinomas have a unique predilection for younger individuals and arise in livers without recognizable liver disease. In contrast to typical hepatocellular carcinomas, fibrolamellar carcinomas show few chromosomal changes and lack mutation in key genes such as TP53 and CTNNB1. Epigenetic instability, manifesting as methylation of important tumor suppressor gene promoters, has not been investigated in fibrolamellar carcinomas. Thus, the methylation status of 11 tumor suppressor gene promoters was investigated using methylation-specific PCR: RASSF1, CDH1, CDKN2B, HPP1, CDKN2A, GSTP1, P16, RARA, FLJ13081, SOCS1, and TP53. Nine fibrolamellar carcinomas were studied including primary tumors (N=5) and metastatic deposits (N=4) along with control groups of typical hepatocellular carcinoma arising in livers with (N=21) and without cirrhosis (N=10). In fibrolamellar carcinomas, RASSF1A and CDH1 (e-cadherin) were the most commonly methylated genes with 80–100% of tumors methylated. However, overall fibrolamellar carcinomas showed low levels of methylation with no differences between fibrolamellar carcinomas and their paired normal livers. However, fibrolamellar carcinomas showed significantly less methylation than hepatocellular carcinomas that arose in the background of viral cirrhosis. Overall, methylation was most strongly linked to viral cirrhosis. In conclusion, fibrolamellar carcinoma shows low levels of methylation. In contrast, higher levels of promoter methylation are associated with hepatocellular carcinomas that arise in the setting of viral induced cirrhosis.
机译:纤维状薄层癌对年轻个体具有独特的嗜好,并且在没有可识别的肝病的肝脏中发生。与典型的肝细胞癌相比,纤维状薄层癌显示出很少的染色体变化,并且在诸如TP53和CTNNB1等关键基因中没有突变。表皮遗传不稳定性表现为重要的肿瘤抑制基因启动子的甲基化,尚未在纤维状层状癌中进行研究。因此,使用甲基化特异性PCR研究了11种肿瘤抑制基因启动子的甲基化状态:RASSF1,CDH1,CDKN2B,HPP1,CDKN2A,GSTP1,P16,RARA,FLJ13081,SOCS1和TP53。研究了九种原发性肿瘤(N = 5)和转移性沉积物(N = 4)以及原发性肝癌(N = 21)和无肝硬化(N = 10)的对照组的9例纤维状薄层癌。在纤维状层状癌中,RASSF1A和CDH1(e-钙黏着蛋白)是最常见的甲基化基因,其中80-100%的肿瘤甲基化。然而,整体纤维状薄层癌显示出低水平的甲基化,而纤维状薄层癌与其配对的正常肝脏之间没有差异。然而,与病毒性肝硬化背景下出现的肝细胞癌相比,纤维状薄层癌的甲基化程度要低得多。总体而言,甲基化与病毒性肝硬化关系最密切。总之,纤维状薄层癌显示出低水平的甲基化。相反,较高水平的启动子甲基化与在病毒性肝硬化的背景下出现的肝细胞癌有关。

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