Whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer
Whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer
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DOI：
10.1038/ng.3547
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发表时间：
2016-05-01
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;Furuta, Mayuko;Nakagawa, Hidewaki
肝癌是一种常见的病毒感染相关疾病，在世界范围内普遍存在，其潜在的病因和基因组结构是异质性的。在这里，我们提供了来自日本个体的300例肝癌的体细胞改变的全基因组景观。我们的综合分析确定了非编码区和编码区的点突变、结构变异（STVs）和病毒整合。我们发现了与肝癌发生相关的突变特征和反复突变的编码区和非编码区，如长基因间非编码RNA基因（NEAT 1和MALAT1），启动子，CTCF结合位点和调控区。STV分析发现了与复制时间的显着关联，并确定了已知的（CDKN2A，CCND1，APC和TERT）和新的（ASH1L，NCOR 1和MACROD2）癌症相关基因，这些基因受到STV的反复影响，导致表达改变。这些结果强调了全基因组测序分析在发现癌症驱动突变和理解肝癌综合分子谱方面的价值，特别是关于STV和非编码突变。
Liver cancer, which is most often associated with virus infection, is prevalent worldwide, and its underlying etiology and genomic structure are heterogeneous. Here we provide a whole-genome landscape of somatic alterations in 300 liver cancers from Japanese individuals. Our comprehensive analysis identified point mutations, structural variations (STVs), and virus integrations, in noncoding and coding regions. We discovered mutational signatures related to liver carcinogenesis and recurrently mutated coding and noncoding regions, such as long intergenic noncoding RNA genes (NEAT1 and MALAT1), promoters, CTCF-binding sites, and regulatory regions. STV analysis found a significant association with replication timing and identified known (CDKN2A, CCND1, APC, and TERT) and new (ASH1L, NCOR1, and MACROD2) cancer-related genes that were recurrently affected by STVs, leading to altered expression. These results emphasize the value of whole-genome sequencing analysis in discovering cancer driver mutations and understanding comprehensive molecular profiles of liver cancer, especially with regard to STVs and noncoding mutations.