Asia-Pacific Journal of Oncology

Research Article | Open Access

Whole-exome sequencing reveals genetic underpinnings of tongue carcinoma in Chinese population

Shuhang Wang1*, Ning Jiang1*, Zicheng Yu2*, Yuan Fang1*, Shujun Xing1, Huiyao Huang1, Yue Yu1, Qi Fan1, Chao Zhang2, Zaixian Tai2, Jiucheng Liu2, Ruixian He3, Ning Li1

1Clinical Trial Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing China.

2GenePlus-Shenzhen, 518000, Shenzhen China.

3Nursing Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing China.
Correspondence: Ning Li (Clinical Trial Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing China; E-mail: Lining@cicams.ac.cn). Ruixian He (Nursing Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing China; E-mail: He87787591@126.com).

Asia-Pacific Journal of Oncology 2020, https://doi.org/10.32948/ajo.2020.10.15

Received: 17 Sep 2020 | Accepted: 10 Oct 2020 | Published online: 19 Oct 2020

Abstract

Oral tongue squamous cell carcinoma (OTSCC) is a common malignancy, of which the incidence has increased in China in the last decade. Surprisingly, while multiple studies have revealed the mutational features of OTSCC in Western populations, limited data was shown in Asian patients. Herein, we utilized whole-exome sequencing to profile the genetic alterations in 13 Chinese OTSCC and compared them to those from 40 Western patients published in Cancer Discovery. In result, some key driver mutations were observed in both Chinese and Western cohorts, such as TP53 (Chinese 60.0% vs Western 60.0%), FAT1 (Chinese 7.7% vs Western 30.0%), CASP8 (Chinese 7.7% vs Western 10.0%) and NOTCH1 (Chinese 15.4% vs Western 10.0%), while mutations in CDKN2A (23.1%) and NTRK3 (23.1%) were only observed in Chinese patients, indicating these two novel mutations might play vital roles in OTSCC tumorigenesis specifically in Asian population. Mutational signatures depicted both common and distinct features across cohorts. In addition, significant copy number loss was found in 7q22.1, 9q13.1, and focal regions spanning CDKN2A and CDKN2B. FOXP1-TEX261 (2p13.3:3p13) fusion, reported in various cancer types, was firstly observed in OTSCC. Also, we identified numerous actionable mutations with FDA approved targeted. Taken together, our study revealed the mutational features of Chinese OTSCC patients, either similar or distinct to those of Caucasian patients. CDKN2A and NTRK3 were observed as two novel drivers that might play essential roles in tumorigenesis in Chinese patients, and were found as two potential therapeutic targets, rendering it promising to develop novel therapies.

Key words Actionable mutation, copy number alteration, oral tongue squamous cell carcinoma, whole-exome sequencing