AUTHOR=Lin Li-Han , Chou Chung-Hsien , Cheng Hui-Wen , Chang Kuo-Wei , Liu Chung-Ji 

TITLE=Precise Identification of Recurrent Somatic Mutations in Oral Cancer Through Whole-Exome Sequencing Using Multiple Mutation Calling Pipelines

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.741626

DOI=10.3389/fonc.2021.741626

ISSN=2234-943X

ABSTRACT=<p>Understanding the genomic alterations in oral carcinogenesis remains crucial for the appropriate diagnosis and treatment of oral squamous cell carcinoma (OSCC). To unveil the mutational spectrum, in this study, we conducted whole-exome sequencing (WES), using six mutation calling pipelines and multiple filtering criteria applied to 50 paired OSCC samples. The tumor mutation burden extracted from the data set of somatic variations was significantly associated with age, tumor staging, and survival. Several genes (<italic>MUC16</italic>, <italic>MUC19</italic>, <italic>KMT2D</italic>, <italic>TTN</italic>, <italic>HERC2</italic>) with a high frequency of false positive mutations were identified. Moreover, known (<italic>TP53</italic>, <italic>FAT1</italic>, <italic>EPHA2</italic>, <italic>NOTCH1</italic>, <italic>CASP8</italic>, and <italic>PIK3CA</italic>) and novel (<italic>HYDIN</italic>, <italic>ALPK3</italic>, <italic>ASXL1</italic>, <italic>USP9X</italic>, <italic>SKOR2</italic>, <italic>CPLANE1</italic>, <italic>STARD9</italic>, and <italic>NSD2</italic>) genes have been found to be significantly and frequently mutated in OSCC. Further analysis of gene alteration status with clinical parameters revealed that canonical pathways, including clathrin-mediated endocytotic signaling, NFκB signaling, PEDF signaling, and calcium signaling were associated with OSCC prognosis. Defining a catalog of targetable genomic alterations showed that 58% of the tumors carried at least one aberrant event that may potentially be targeted by approved therapeutic agents. We found molecular OSCC subgroups which were correlated with etiology and prognosis while defining the landscape of major altered events in the coding regions of OSCC genomes. These findings provide information that will be helpful in the design of clinical trials on targeted therapies and in the stratification of patients with OSCC according to therapeutic efficacy.</p>