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Identification of driver genes in hepatocellular carcinoma by exome sequencing
Author(s) -
Cleary Sean P.,
Jeck William R.,
Zhao Xiaobei,
Chen Kui,
Selitsky Sara R.,
Savich Gleb L.,
Tan TingXu,
Wu Michael C.,
Getz Gad,
Lawrence Michael S.,
Parker Joel S.,
Li Jinyu,
Powers Scott,
Kim Hyeja,
Fischer Sandra,
Guindi Maha,
Ghanekar Anand,
Chiang Derek Y.
Publication year - 2013
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.26540
Subject(s) - nonsynonymous substitution , exome sequencing , biology , exome , genetics , gene , hepatocellular carcinoma , mutation , cancer research , methyltransferase , hccs , histone , histone methyltransferase , methylation , genome
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. (H epatology 2013;58:1693–1702)