Identification of driver genes in hepatocellular carcinoma by exome sequencing.
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.
Duke Scholars
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- Sequence Analysis, DNA
- NF-E2-Related Factor 2
- Myeloid-Lymphoid Leukemia Protein
- Mutation
- Middle Aged
- Male
- Liver Neoplasms
- Kelch-Like ECH-Associated Protein 1
- Intracellular Signaling Peptides and Proteins
- Humans
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Sequence Analysis, DNA
- NF-E2-Related Factor 2
- Myeloid-Lymphoid Leukemia Protein
- Mutation
- Middle Aged
- Male
- Liver Neoplasms
- Kelch-Like ECH-Associated Protein 1
- Intracellular Signaling Peptides and Proteins
- Humans