Oncotarget

Research Papers:

Differences in somatic mutation landscape of hepatocellular carcinoma in Asian American and European American populations

Song Yao _, Christopher Johnson, Qiang Hu, Li Yan, Biao Liu, Christine B. Ambrosone, Jianmin Wang and Song Liu

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Oncotarget. 2016; 7:40491-40499. https://doi.org/10.18632/oncotarget.9636

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Abstract

Song Yao1,*, Christopher Johnson2,*, Qiang Hu2, Li Yan2, Biao Liu2, Christine B. Ambrosone1, Jianmin Wang2, Song Liu2

1Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA

2Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY, USA

*These authors have contributed equally to this work

Correspondence to:

Song Yao, email: song.yao@roswellpark.org

Jianmin Wang, email: jianmin.wang@roswellpark.org

Song Liu, email: song.liu@roswellpark.org

Keywords: somatic mutation, hepatocellular carcinoma, disparity, TCGA, ancestry

Received: March 05, 2016     Accepted: May 09, 2016     Published: May 26, 2016

ABSTRACT

The incidence rate of hepatocellular carcinoma (HCC) is higher in populations of Asian ancestry than European ancestry (EA). We sought to investigate HCC mutational differences between the two populations, which may reflect differences in the prevalence of etiological factors. We compared HCC somatic mutations in patients of self-reported Asian American and EA from The Cancer Genome Atlas (TCGA), and assessed associations of tumor mutations with established HCC risk factors. Although the average mutation burden was similar, TP53 and RB1 were mutated at a much higher frequency in Asian Americans than in EAs (TP53: 43% vs. 21%; RB1: 19% vs. 2%). Three putative oncogenic genes, including TRPM3, SAGE1, and ADAMTS7, were mutated exclusively in Asians. In addition, VEGF binding pathway, a druggable target by tyrosine kinase inhibitors such as sorafenib, was mutated at a higher frequency among Asians (13% vs. 2%); while the negative regulation of IL17 production, involved in inflammation and autoimmunity, was mutated only in EAs (12% vs. 0). Accounting for HCC risk factors had little impact on any of the mutational differences. In conclusion, we demonstrated here mutational differences in important cancer genes and pathways between Asian and European ancestries. These differences may have implications for the prevention and treatment of HCC.


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