Decoding complex patterns of genomic rearrangement in hepatocellular carcinoma

被引：46

作者：

Fernandez-Banet, Julio ^{[1
]}

Lee, Nikki P. ^{[2
]}

Chan, Kin Tak ^{[2
]}

Gao, Huan ^{[3
]}

Liu, Xiao ^{[3
,4
]}

Sung, Wing-Kin ^{[5
,6
]}

Tan, Winnie ^{[2
]}

Fan, Sheung Tat ^{[2
]}

Poon, Ronnie T. ^{[2
]}

Li, Shiyong ^{[3
]}

Ching, Keith ^{[1
]}

Rejto, Paul A. ^{[1
]}

Mao, Mao ^{[1
,7
]}

Kan, Zhengyan ^{[1
]}

机构：

[1] Pfizer Oncol, San Diego, CA USA

[2] Univ Hong Kong, Dept Surg, Hong Kong, Hong Kong, Peoples R China

[3] BGI Shenzhen, Shenzhen, Peoples R China

[4] Univ Copenhagen, Dept Biol, Copenhagen, Denmark

[5] Natl Univ Singapore, Sch Comp, Singapore 117548, Singapore

[6] Genome Inst Singapore, Singapore, Singapore

[7] Asian Canc Res Grp Inc, Wilmington, DE USA

来源：

GENOMICS | 2014年 / 103卷 / 2-3期

关键词：

Genomic rearrangement; Hepatocellular carcinoma; Whole-genome sequencing; Copy number variation; GENE FUSIONS; STRUCTURAL VARIATION; RECURRENT MUTATIONS; CANCER; MEGALIN; EXPRESSION; IDENTIFICATION; PATHOGENESIS; INSIGHTS; RECEPTOR;

D O I：

10.1016/j.ygeno.2014.01.003

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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.

引用

页码：189 / 203

页数：15

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