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

Journal of Thoracic Disease

article

Guixiang Weng¹  Wei Zhao³  Yanwei Yin²  Suzhen Wang³  Lei Du²  Ning Liu³  Dianbin Mu³  Qingxi Yu³  Shuanghu Yuan⁴ 

[1] Shandong University;Department of Oncology of Linyi People’s Hospital;Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences;Shandong Cancer Hospital and Institute-Shandong Cancer Hospital Affiliated to Shandong University

关键词: Whole-exome sequencing (WES);    radiotherapy;    gene mutation profile;    esophageal squamous cell carcinoma (ESCC);   

DOI  :  10.21037/jtd-20-2450

学科分类：呼吸医学

来源: Pioneer Bioscience Publishing Company

【 摘 要 】

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.

【 授权许可】

Unknown