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Abstract 4598: Identification of driver genes in hepatocellular carcinoma by exome sequencing.

Publication ,  Conference
Cleary, SP; Jeck, WR; Zhao, X; Selitsky, SR; Savich, GL; Tan, T-X; Wu, MC; Getz, G; Lawrence, MS; Parker, JS; Li, J; Powers, S; Kim, H ...
Published in: Cancer Research
April 15, 2013

Genetic alterations in specific driver genes lead to disruption of cellular pathways and are critical events in the instigation and progression of hepatocellular carcinoma. As a prerequisite for individualized cancer treatment, we sought to characterize the landscape of recurrent somatic mutations in hepatocellular carcinoma. We performed whole exome sequencing on 87 hepatocellular carcinomas and matched normal adjacent tissues to an average coverage of 59x. The overall mutation rate was roughly 2.5 mutations per Mb, with a median of 45 non-synonymous mutations that altered the amino acid sequence (range 2 to 381). We found recurrent mutations in several genes with high transcript levels: TP53 (20%), CTNNB1 (15%), IGSF3 (9%) and KEAP1 (8%). 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. Clinical data demonstrated significantly decreased disease-free survival in tumors with p53 mutations (p=0.006) and a trend was observed towards higher rates of recurrence and shorter disease free survival among MLL mutation carriers. The NFE2L2-KEAP1 and MLL pathways are recurrently mutated in multiple cohorts of hepatocellular carcinoma. The elucidation of genetic changes in HCC will enhance our understanding of hepatocarcinogenesis and influence disease prognosis and therapy.Citation Format: Sean P. Cleary, William R. Jeck, Xiaobei Zhao, Sara R. Selitsky, Gleb L. Savich, Ting-Xu Tan, Michael C. Wu, Gad Getz, Michael S. Lawrence, Joel S. Parker, Jinyu Li, Scott Powers, Hyeja Kim, Sandra E. Fischer, Maha Guindi, Anand Ghanekar, Derek Y. Chiang. Identification of driver genes in hepatocellular carcinoma by exome sequencing. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4598. doi:10.1158/1538-7445.AM2013-4598

Duke Scholars

Published In

Cancer Research

DOI

EISSN

1538-7445

ISSN

0008-5472

Publication Date

April 15, 2013

Volume

73

Issue

8_Supplement

Start / End Page

4598 / 4598

Publisher

American Association for Cancer Research (AACR)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis
 

Citation

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Cleary, S. P., Jeck, W. R., Zhao, X., Selitsky, S. R., Savich, G. L., Tan, T.-X., … Chiang, D. Y. (2013). Abstract 4598: Identification of driver genes in hepatocellular carcinoma by exome sequencing. In Cancer Research (Vol. 73, pp. 4598–4598). American Association for Cancer Research (AACR). https://doi.org/10.1158/1538-7445.am2013-4598
Cleary, Sean P., William R. Jeck, Xiaobei Zhao, Sara R. Selitsky, Gleb L. Savich, Ting-Xu Tan, Michael C. Wu, et al. “Abstract 4598: Identification of driver genes in hepatocellular carcinoma by exome sequencing.” In Cancer Research, 73:4598–4598. American Association for Cancer Research (AACR), 2013. https://doi.org/10.1158/1538-7445.am2013-4598.
Cleary SP, Jeck WR, Zhao X, Selitsky SR, Savich GL, Tan T-X, et al. Abstract 4598: Identification of driver genes in hepatocellular carcinoma by exome sequencing. In: Cancer Research. American Association for Cancer Research (AACR); 2013. p. 4598–4598.
Cleary, Sean P., et al. “Abstract 4598: Identification of driver genes in hepatocellular carcinoma by exome sequencing.Cancer Research, vol. 73, no. 8_Supplement, American Association for Cancer Research (AACR), 2013, pp. 4598–4598. Crossref, doi:10.1158/1538-7445.am2013-4598.
Cleary SP, Jeck WR, Zhao X, Selitsky SR, Savich GL, Tan T-X, Wu MC, Getz G, Lawrence MS, Parker JS, Li J, Powers S, Kim H, Fischer SE, Guindi M, Ghanekar A, Chiang DY. Abstract 4598: Identification of driver genes in hepatocellular carcinoma by exome sequencing. Cancer Research. American Association for Cancer Research (AACR); 2013. p. 4598–4598.

Published In

Cancer Research

DOI

EISSN

1538-7445

ISSN

0008-5472

Publication Date

April 15, 2013

Volume

73

Issue

8_Supplement

Start / End Page

4598 / 4598

Publisher

American Association for Cancer Research (AACR)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis