Cleary, S. P., Jeck, W. R., Zhao, X. B., Chen, K., Selitsky, S. R., Savich, G. L., Tan, T. X., Wu, M. C., Getz, G., Lawrence, M. S., Parker, J. S., Li, J. Y., Powers, S., Kim, H., Fischer, S., Guindi, M., Ghanekar, A., Chiang, D. Y. (November 2013) Identification of Driver Genes in Hepatocellular Carcinoma by Exome Sequencing. Hepatology, 58 (5). pp. 1693-1702. ISSN 0270-9139
Abstract
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 59x. 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. (Hepatology 2013;58:1693-1702)
Actions (login required)
 |
Administrator's edit/view item |