Genetics and epigenetics of liver cancer
Genetics and epigenetics of liver cancer
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DOI：
10.1016/j.nbt.2013.01.007
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发表时间：
2013-05-25
影响因子：
5.4
通讯作者：
Ozturk, Mehmet
中科院分区：
文献类型：
--
作者：
Ozen, Cigdem;Yildiz, Gokhan;Ozturk, Mehmet
肝细胞癌（HCC）是成人原发性肝癌的主要形式。慢性B肝炎（HBV）和丙型肝炎（HCV）病毒感染和酗酒是导致肝癌的主要因素。这种致命的癌症影响了全世界50多万人，它对传统的化疗和放疗具有很强的抵抗力。肝癌的遗传学和表观遗传学研究有助于更好地了解其发病机制，并为肝癌的早期诊断和治疗提供新的工具。最近的文献对肝癌的全基因组分析表明，除了已知的基因如TP53，CTNNB1，AXIN1和CDKN2A之外，还有大量的突变基因，但它们的频率要低得多。除了CTNNB1突变，大多数其他突变似乎导致功能丧失。因此，HCC相关突变不能容易地靶向治疗。表观遗传畸变似乎发生得相当频繁，可能成为新的目标。全球DNA低甲基化，启动子甲基化，非编码RNA的异常表达和其他表观遗传调控基因（如EZH2）的表达失调是最著名的表观遗传异常。未来在这一方向的研究可能有助于确定新的生物标志物和HCC的治疗靶点。
Hepatocellular carcinoma (HCC) represents a major form of primary liver cancer in adults. Chronic infections with hepatitis B (HBV) and C (HCV) viruses and alcohol abuse are the major factors leading to HCC. This deadly cancer affects more than 500,000 people worldwide and it is quite resistant to conventional chemo- and radiotherapy. Genetic and epigenetic studies on HCC may help to understand better its mechanisms and provide new tools for early diagnosis and therapy. Recent literature on whole genome analysis of HCC indicated a high number of mutated genes in addition to well-known genes such as TP53, CTNNB1, AXIN1 and CDKN2A, but their frequencies are much lower. Apart from CTNNB1 mutations, most of the other mutations appear to result in loss-of-function. Thus, HCC-associated mutations cannot be easily targeted for therapy. Epigenetic aberrations that appear to occur quite frequently may serve as new targets. Global DNA hypomethylation, promoter methylation, aberrant expression of non-coding RNAs and dysregulated expression of other epigenetic regulatory genes such as EZH2 are the best-known epigenetic abnormalities. Future research in this direction may help to identify novel biomarkers and therapeutic targets for HCC.