Identification of driver genes in hepatocellular carcinoma by exome sequencing.
Hepatology
; 58(5): 1693-702, 2013 Nov.
Article
in En
| MEDLINE
| ID: mdl-23728943
ABSTRACT
UNLABELLED Genetic alterations in specific driver genes lead to disruption of cellular pathways and are critical events in the instigation and progression of hepatocellular carcinoma (HCC). As a prerequisite for individualized cancer treatment, we sought to characterize the landscape of recurrent somatic mutations in HCC. We performed whole-exome sequencing on 87 HCCs and matched normal adjacent tissues to an average coverage of 59×. The overall mutation rate was roughly two mutations per Mb, with a median of 45 nonsynonymous mutations that altered the amino acid sequence (range, 2-381). We found recurrent mutations in several genes with high transcript levels TP53 (18%); CTNNB1 (10%); KEAP1 (8%); C16orf62 (8%); MLL4 (7%); and RAC2 (5%). Significantly affected gene families include the nucleotide-binding domain and leucine-rich repeat-containing family, calcium channel subunits, and histone methyltransferases. In particular, the MLL family of methyltransferases for histone H3 lysine 4 were mutated in 20% of tumors. CONCLUSION:
The NFE2L2-KEAP1 and MLL pathways are recurrently mutated in multiple cohorts of HCC.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carcinoma, Hepatocellular
/
Exome
/
Liver Neoplasms
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Adolescent
/
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Hepatology
Year:
2013
Type:
Article
Affiliation country:
Canada