Whole-genome sequencing of liver cancers identifies etiological influences on mutation patterns and recurrent mutations in chromatin regulators
Whole-genome sequencing of liver cancers identifies etiological influences on mutation patterns and recurrent mutations in chromatin regulators
复制标题
DOI：
10.1038/ng.2291
复制
发表时间：
2012-07-01
期刊：
影响因子：
30.8
通讯作者：
Nakagawa, Hidewaki
中科院分区：
文献类型：
--
作者：
Fujimoto, Akihiro;Totoki, Yasushi;Nakagawa, Hidewaki
肝细胞癌（HCC）是全球第三大癌症相关死亡原因。我们对27例HCC的全基因组进行了测序和分析，其中25例与B或C型肝炎病毒感染有关，包括两组多中心肿瘤。虽然在多中心肿瘤对中没有发现常见的体细胞突变，但它们的全基因组取代模式相似，表明这些肿瘤是从独立的突变发展而来的，尽管它们共同的病因学背景可能强烈影响了它们的体细胞突变模式。统计和功能分析产生了一系列反复突变的基因。多种染色质调节因子，包括ARID1A、ARID1B、ARID2、MLL和MLL3，在50%的肿瘤中发生突变。B型肝炎病毒基因组整合在TERT基因座经常观察到高克隆比例。我们对HCC的全基因组测序分析确定了病因背景对体细胞突变模式和随后的致癌作用的影响，以及HCC中染色质调节因子的复发性突变。
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. We sequenced and analyzed the whole genomes of 27 HCCs, 25 of which were associated with hepatitis B or C virus infections, including two sets of multicentric tumors. Although no common somatic mutations were identified in the multicentric tumor pairs, their whole-genome substitution patterns were similar, suggesting that these tumors developed from independent mutations, although their shared etiological backgrounds may have strongly influenced their somatic mutation patterns. Statistical and functional analyses yielded a list of recurrently mutated genes. Multiple chromatin regulators, including ARID1A, ARID1B, ARID2, MLL and MLL3, were mutated in similar to 50% of the tumors. Hepatitis B virus genome integration in the TERT locus was frequently observed in a high clonal proportion. Our whole-genome sequencing analysis of HCCs identified the influence of etiological background on somatic mutation patterns and subsequent carcinogenesis, as well as recurrent mutations in chromatin regulators in HCCs.