Decoding complex patterns of genomic rearrangement in hepatocellular carcinoma
Decoding complex patterns of genomic rearrangement in hepatocellular carcinoma
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DOI：
10.1016/j.ygeno.2014.01.003
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发表时间：
2014-02-01
期刊：
影响因子：
4.4
通讯作者：
Kan, Zhengyan
中科院分区：
文献类型：
--
作者：
Fernandez-Banet, Julio;Lee, Nikki P.;Kan, Zhengyan
阐明肝细胞癌（HCC）的分子基础对于开发针对这种致命疾病的靶向诊断和治疗方法至关重要。体细胞基因组重排（GRs）的情况在肝细胞癌中尚未得到充分表征，而基因组重排可导致致癌基因融合。我们基于88例原发性肝细胞癌肿瘤/非肿瘤组织的全基因组测序数据，预测了4314种基因组重排，包括大规模插入、缺失、倒位和易位。我们在5个肝细胞癌基因组（5.7%）中发现了染色体碎裂现象，其反复影响染色体臂1q和8q。发现10%的队列中白蛋白（ALB）存在基因组重排、失活突变和缺失。综合分析确定了一种成对的染色体内易位模式，其两侧为局灶性扩增，以及一种拷贝数变异的不对称模式，其位于易位断点两侧。此外，我们预测了260种基因融合，这些融合经常导致肿瘤中3'基因异常过度表达，并验证了18种基因融合，包括ABCB11和LRP2的反复融合（2/88）。（C）2014作者。由爱思唯尔公司出版。保留所有权利。
Elucidating the molecular basis of hepatocellular carcinoma (HCC) is crucial to developing targeted diagnostics and therapies for this deadly disease. The landscape of somatic genomic rearrangements (GRs), which can lead to oncogenic gene fusions, remains poorly characterized in HCC. We have predicted 4314 GRs including large-scale insertions, deletions, inversions and translocations based on the whole-genome sequencing data for 88 primary HCC tumor/non-tumor tissues. We identified chromothripsis in 5 HCC genomes (5.7%) recurrently affecting chromosomal arms 1q and 8q. Albumin (ALB) was found to harbor GRs, deactivating mutations and deletions in 10% of cohort Integrative analysis identified a pattern of paired intra-chromosomal translocations flanking focal amplifications and asymmetrical patterns of copy number variation flanking breakpoints of translocations. Furthermore, we predicted 260 gene fusions which frequently result in aberrant over-expression of the 3' genes in tumors and validated 18 gene fusions, including recurrent fusion (2/88) of ABCB11 and LRP2. (C) 2014 The Authors. Published by Elsevier Inc All rights reserved.