Differences in somatic mutation landscape of hepatocellular carcinoma in Asian American and European American populations
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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
Song Yao, email: firstname.lastname@example.org
Jianmin Wang, email: email@example.com
Song Liu, email: firstname.lastname@example.org
Keywords: somatic mutation, hepatocellular carcinoma, disparity, TCGA, ancestry
Received: March 05, 2016 Accepted: May 09, 2016 Published: May 26, 2016
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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