Exome sequencing identifies new somatic alterations and mutation patterns of tongue squamous cell carcinoma in a Chinese population

Exome sequencing identifies new somatic alterations and mutation patterns of tongue squamous cell carcinoma in a Chinese population:

Abstract

Tongue squamous cell carcinoma (TSCC) is an aggressive group of tumors characterized by high rates of regional lymph node metastasis and local recurrence. Emerging evidence has revealed genetic variations of TSCC across different geographical regions due to the impact of multiple risk factors such as chewing betel‐quid. However, we know little of the mutational processes of TSCC in the Chinese population without the history of chewing betel‐quid/tobacco. To explore the mutational spectrum of this disease, we performed whole‐exome sequencing of sample pairs, comprising tumors and normal tissue, from 82 TSCC patients. In addition to identifying seven previously known TSCC‐associated genes (TP53 , CDKN2A , PIK3CA , NOTCH1 , ASXL1 , USH2A and CSMD3 ), the analysis revealed six new genes (GNAQ , PRG4 , RP1 , ZNF16 , NBEA and PTPRC ) that had not been previously been reported in TSCC. Our in vitro experiments identified ZNF16 for the first time as a solid tumor associated gene to promote malignancy of TSCC cells. We also identified a microRNA (miR‐585‐5p) encoded by the 5q35.1 region and characterized it as a tumor suppressor by targeting SOX9 . At least one non‐silent mutation of genes involved in the ten canonical oncogenic pathways (Notch, RTK‐RAS, PI3K, Wnt, Cell cycle, p53, Myc, Hippo, TGFß and Nrf2) was found in 82.9% of cases. Collectively, our data extend the spectrum of TSCC mutations and define novel diagnosis markers and potential clinical targets for TSCC.

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