Comparative genomic analysis of esophageal squamous cell carcinoma between Asian and Caucasian patient populations.

Deng J1,2, Chen H3,4, Zhou D5,6, Zhang J1,2, Chen Y1,2, Liu Q1,2, Ai D1,2, Zhu H1,2, Chu L1,2, Ren W1,2, Zhang X1,2, Xia Y1,2, Sun M2,7, Zhang H8, Li J4, Peng X4, Li L9, Han L8, Lin H5,6, Cai X5,6, Xiang J10, Chen S10, Sun Y10, Zhang Y10, Zhang J10, Chen H10, Zhang S11, Zhao Y11, Liu Y12, Liang H13,14,15, Zhao K16,17.

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Abstract

Esophageal squamous cell carcinoma is a major histological type of esophageal cancer, with distinct incidence and survival patterns among races. Although previous studies have characterized somatic mutations in this disease, a rigorous comparison between different patient populations has not been conducted. Here we sequence the samples of 316 Chinese patients, combine them with those from The Cancer Genome Atlas, and perform a comparative analysis between Asian and Caucasian patients. We find that mutated CSMD3 is associated with better prognosis in Asian patients. Applying a robust computational strategy that adjusts for both technical and biological confounding factors, we find that TP53, EP300, and NFE2L2 show higher mutational frequencies in Asian patients. Moreover, NFE2L2 mutations correlate with the allele status of a nearby high-Fst SNP, suggesting their potential interaction. Our study provides insights into the molecular basis underlying the striking racial disparities of this disease, and represents a general computational framework for such a cross-population comparison.