Diverse modes of genomic alteration in hepatocellular carcinoma

Genome Biology
Suchit JhunjhunwalaZemin Zhang

Abstract

Hepatocellular carcinoma (HCC) is a heterogeneous disease with high mortality rate. Recent genomic studies have identified TP53, AXIN1, and CTNNB1 as the most frequently mutated genes. Lower frequency mutations have been reported in ARID1A, ARID2 and JAK1. In addition, hepatitis B virus (HBV) integrations into the human genome have been associated with HCC. Here, we deep-sequence 42 HCC patients with a combination of whole genome, exome and transcriptome sequencing to identify the mutational landscape of HCC using a reasonably large discovery cohort. We find frequent mutations in TP53, CTNNB1 and AXIN1, and rare but likely functional mutations in BAP1 and IDH1. Besides frequent hepatitis B virus integrations at TERT, we identify translocations at the boundaries of TERT. A novel deletion is identified in CTNNB1 in a region that is heavily mutated in multiple cancers. We also find multiple high-allelic frequency mutations in the extracellular matrix protein LAMA2. Lower expression levels of LAMA2 correlate with a proliferative signature, and predict poor survival and higher chance of cancer recurrence in HCC patients, suggesting an important role of the extracellular matrix and cell adhesion in tumor progression of a subgroup of ...Continue Reading

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Nov 15, 2015·Journal of Cellular Physiology·Justin T HuntingtonGustavo Leone
Nov 14, 2016·Carcinogenesis·Chinthalapally V RaoHiroshi Y Yamada
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Datasets Mentioned

BETA
GSE25097
EGAS00001000824
EGAS00001000678

Methods Mentioned

BETA
RNA-Seq
exome-sequencing
PCR
Hi-Seq
DNA-Seq

Related Concepts

Lama2 protein, mouse
DNA Mutational Analysis
Hepatitis B
Dane Particle
Liver Carcinoma
Merosin
Malignant Neoplasm of Liver
Variation (Genetics)
Survival Analysis
Genetic Heterogeneity

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