Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma. - Archive ouverte HAL Access content directly
Journal Articles Nature Genetics Year : 2012

Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma.

(1, 2) , (1, 2) , (1, 2) , (1, 2) , (1, 2) , (1, 2) , (1, 2, 3) , (4, 5) , (6) , (7) , (8) , (4, 5) , (5) , (9) , (1, 2) , (10) , (11) , (1, 2, 12)
1
2
3
4
5
6
7
8
9
10
11
12
Mélanie Letexier
  • Function : Author
Eric Chevet
Alexis Laurent
Eric Letouzé

Abstract

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. Here, we performed high-resolution copy-number analysis on 125 HCC tumors and whole-exome sequencing on 24 of these tumors. We identified 135 homozygous deletions and 994 somatic mutations of genes with predicted functional consequences. We found new recurrent alterations in four genes (ARID1A, RPS6KA3, NFE2L2 and IRF2) not previously described in HCC. Functional analyses showed tumor suppressor properties for IRF2, whose inactivation, exclusively found in hepatitis B virus (HBV)-related tumors, led to impaired TP53 function. In contrast, inactivation of chromatin remodelers was frequent and predominant in alcohol-related tumors. Moreover, association of mutations in specific genes (RPS6KA3-AXIN1 and NFE2L2-CTNNB1) suggested that Wnt/β-catenin signaling might cooperate in liver carcinogenesis with both oxidative stress metabolism and Ras/mitogen-activated protein kinase (MAPK) pathways. This study provides insight into the somatic mutational landscape in HCC and identifies interactions between mutations in oncogene and tumor suppressor gene mutations related to specific risk factors.
Fichier principal
Vignette du fichier
Sup_Table_and_Fig.pdf (3.03 Mo) Télécharger le fichier
Vignette du fichier
32996_0_merged_1323686834.pdf (1.04 Mo) Télécharger le fichier
Vignette du fichier
inserm-00719917_edited.pdf (521.39 Ko) Télécharger le fichier
Origin : Files produced by the author(s)
Origin : Files produced by the author(s)
Origin : Files produced by the author(s)

Dates and versions

inserm-00719917 , version 1 (01-10-2012)

Identifiers

Cite

Cécile Guichard, Giuliana Amaddeo, Sandrine Imbeaud, Yannick Ladeiro, Laura Pelletier, et al.. Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma.: Genetic landscape of hepatocellular carcinoma. Nature Genetics, 2012, 44 (6), pp.694-8. ⟨10.1038/ng.2256⟩. ⟨inserm-00719917⟩
924 View
2160 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More