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

Jessica Zucman-Rossi and colleagues report exome sequencing of 24 hepatocellular carcinomas and non-tumor liver tissues and copy-number analysis of 125 tumors. They identify new recurrent mutations in ARID1A , RPS6KA3 , NFE2L2 and IRF2 in HCC. Hepatocellular carcinoma (HCC) is the most common primar...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Nature genetics Jg. 44; H. 6; S. 694 - 698
Hauptverfasser: Guichard, Cécile, Amaddeo, Giuliana, Imbeaud, Sandrine, Ladeiro, Yannick, Pelletier, Laura, Maad, Ichrafe Ben, Calderaro, Julien, Bioulac-Sage, Paulette, Letexier, Mélanie, Degos, Françoise, Clément, Bruno, Balabaud, Charles, Chevet, Eric, Laurent, Alexis, Couchy, Gabrielle, Letouzé, Eric, Calvo, Fabien, Zucman-Rossi, Jessica
Format: Journal Article
Sprache:Englisch
Veröffentlicht: New York Nature Publishing Group US 01.06.2012
Nature Publishing Group
Nature Pub. Co
Schlagworte:
631/208/2489/144
631/208/69
Agriculture
Alcohol use
Animal Genetics and Genomics
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Cancer
Cancer Research
Carcinogenesis
Carcinoma, Hepatocellular - genetics
Chromosomes
Copy number variations
DNA Copy Number Variations
Fundamental and applied biological sciences. Psychology
Gastroenterology. Liver. Pancreas. Abdomen
Gene expression
Gene Function
Gene mutations
Genetic aspects
Genetics of eukaryotes. Biological and molecular evolution
Genomes
Health aspects
Hepatitis B virus
Hepatoma
Human Genetics
Humans
Inactivation
Interferon Regulatory Factor-2 - genetics
letter
Liver cancer
Liver Neoplasms - genetics
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Medical sciences
Mutation
Oxidative stress
Risk factors
Signal Transduction - genetics
Tumors
France
Somatic mutation
Gene
Digestive system
Copy number
Liver
Digestive diseases
Hepatic disease
Hepatocellular carcinoma
Identification
Malignant tumor
Cancer
ISSN:1061-4036, 1546-1718, 1546-1718
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Jessica Zucman-Rossi and colleagues report exome sequencing of 24 hepatocellular carcinomas and non-tumor liver tissues and copy-number analysis of 125 tumors. They identify new recurrent mutations in ARID1A , RPS6KA3 , NFE2L2 and IRF2 in HCC. 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.
Bibliographie:ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
content type line 14
ObjectType-Article-1
ObjectType-Feature-2
content type line 23
ISSN:1061-4036
1546-1718
1546-1718
DOI:10.1038/ng.2256