Decoding complex patterns of genomic rearrangement in hepatocellular carcinoma.

Abstract:

: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.

journal_name

Genomics

journal_title

Genomics

authors

Fernandez-Banet J,Lee NP,Chan KT,Gao H,Liu X,Sung WK,Tan W,Fan ST,Poon RT,Li S,Ching K,Rejto PA,Mao M,Kan Z

doi

10.1016/j.ygeno.2014.01.003

subject

Has Abstract

pub_date

2014-02-01 00:00:00

pages

189-203

issue

2-3

eissn

0888-7543

issn

1089-8646

pii

S0888-7543(14)00004-4

journal_volume

103

pub_type

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