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Identification of mutations in cancer predisposition genes in radiosensitive and radioresistant patients with nasopharyngeal carcinoma

Xingwen Wang, Yunyan Wu, Qiang Li, Dongxiao Lv, Junqing Han, Ping Liu

The objective of the present study was to determine whether the alterations of cancer predisposition genes were different between radiosensitive and radioresistant patients with Nasopharyngeal Carcinoma (NPC). A total of 21 patients with nasopharyngeal carcinoma were included in this study. All patients were treated with standardized radiotherapy. Sixteen of the tumors were clinically radiosensitive and 5 were radioresistant. Genomic DNA, extracted from Formalin-Fixed Paraffin-Embedded (FFPE) tumor specimens obtained prior to treatment, was subjected to amplicon-based Next-Generation Sequencing (NGS) with primer sets targeting 50 critical human tumor suppressor genes and oncogenes. We identified 18 nonsynonymous mutations, 1 nonframeshift deletion and 1 frameshift mutation distributed across 15 genes, including 11 mutations have been reported in COSMIC (the Catalogue of Somatic Mutations in Cancer) or dbSNP database (database of single nucleotide polymorphisms), and 9 novel mutations. Most of these mutations have not been reported in NPC. More importantly, 5 radiosensitivespecific mutations targeting AKT1, PIK3CA, MET, TP53 and STK11 were observed, suggesting the genetic alterations of PI3K/AKT and p53 pathways were involved in the response to radiotherapy. Collectively, genetic mutations may differentiate tumor radiosensitivity and radioresistance, although validation of such mutations using a large sample size cohort is necessary before a solid conclusion can be reached.