Genomic alterations of whole exome sequencing in esophageal squamous cell carcinoma before and after radiotherapy

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is among the leading causes of cancer mortality, especially in China. Advances in technology have resulted in significant clinical gains in the treatment of ESCC, with more precise radiotherapy now considered an integral part of standard patient care, either alone or in combination with chemotherapy. Though, a better understanding of tumoral radiosensitivity is still needed in order to develop strategies and further personalize radiation treatments. METHODS: We carried out whole-exome sequencing (WES) on paired tumors collected before and after radiotherapy from 11 patients with ESCC. A comprehensive analysis was performed to compare the somatic mutations, the driver genes mutations, the copy number variations (CNVs), the mutational signatures, the tumor’s clonal composition, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway between pre- and post-radiotherapy samples in this cohort. RESULTS: According to the analysis of WES results, more insertion/deletion mutations (indels) were discovered in the post-radiotherapy samples than in the pre-radiotherapy samples (Wilcoxon rank-sum test, P=0.014). The mutation rate of driver gene Ephrin-A2 (EPHA2) was significantly reduced after radiotherapy (Fisher’s exact test, P=0.035). However, comparison between the pre- and post-radiotherapy groups reveals no significant differences in other content. CONCLUSIONS: Our study revealed the overall genomic profile of ESCC before and after radiotherapy and determined that a loss of EPHA2 mutations might make cancer cells resistance to radiotherapy.