Abstract
Somatic mutation analysis is a standard practice in the study of human cancers to identify mutations that cause therapeutic sensitization and resistance. We performed comprehensive genomic analyses that used PCR target enrichment and next-generation sequencing on Ion Proton semiconductor sequencers. Forty-seven oral squamous cell carcinoma (OSCC) samples and their corresponding noncancerous tissues were used for multiplex PCR amplification to obtain targeted coverage of the entire coding regions of 409 cancer-related genes (covered regions: 95.4% of total, 1.69 megabases of target sequence). The number of somatic mutations in 47 patients with OSCC ranged from 1 to 20 with a mean of 7.60. The most frequent mutations were in TP53 (61.7%), NOTCH1 (25.5%), CDKN2A (19.1%), SYNE1 (14.9%), PIK3CA (10.6%), ROS1 (10.6%), and TAF1L (10.6%). We also detected copy number variations (CNVs) in the segments of the genome that could be duplicated or deleted from deep sequencing data. Pathway assessment showed that the somatic aberrations within OSCC genomes are mainly involved in several important pathways, including cell cycle regulation and RTK–MAPK-PI3K. This study may enable better selection of therapies and deliver improved outcomes for OSCC patients when combined with clinical diagnostics.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy in developed countries, representing nearly 2.4% of all malignancies [1]
The poor prognosis of oral squamous cell carcinoma (OSCC) patients is associated with the overexpression of anti-apoptotic genes and the deregulation of p53 function [2,3,4], both of which may contribute to chemotherapy resistance
C>T transitions were the most common mutations found in HNSCC and esophageal squamous cell carcinoma (ESCC) in previous whole exome sequencing studies (Supplementary Figure 2)
Summary
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy in developed countries, representing nearly 2.4% of all malignancies [1]. Oral squamous cell carcinoma (OSCC), a subset of HNSCC, accounts for > 90% of malignancies that affect the oral cavity. The etiology of OSCC is well established and mainly involves the use of tobacco and alcohol. Many published studies have evaluated markers of the cell cycle, the immune response, apoptosis, and angiogenesis as well as adhesion- and matrix degradation-related molecules. The poor prognosis of OSCC patients is associated with the overexpression of anti-apoptotic genes and the deregulation of p53 function [2,3,4], both of which may contribute to chemotherapy resistance. The precise molecular mechanism underlying the resistance to chemotherapy displayed by recurrent OSCC remains largely unknown
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