Computational studies reveal co-occurrence of two mutations in IL7R gene of high-grade serous carcinoma patients

Major cause of mortality in ovarian cancer can be attributed to a lack of specific and sensitive biomarkers for diagnosis and prognosis of the disease. Uncovering the mutations in genes involved in crucial oncogenic pathways is a key step in discovery and development of novel biomarkers. Whole exome sequencing (WES) is a powerful method for the detection of cancer driver mutations. The present work focuses on identifying functionally damaging mutations in patients with high-grade serous ovarian carcinoma (HGSC) through computational analysis of WES. In this study, WES data of HGSC patients was retrieved from the genomic literature available in sequence read archive, the variants were identified and comprehensive structural and functional analysis was performed. Interestingly, I66T and V138I mutations were found to be co-occurring in the IL7R gene in four out of five HGSC patient samples investigated in this study. The V138I mutation was located in the fibronectin type-3 domain and computationally assessed to be causing disruptive effects on the structure and dynamics of IL7R protein. This mutation was found to be co-occurring with the neutral I66T mutation in the same domain which compensated the disruptive effects of V138I variant. These comprehensive studies point to a hitherto unexplored significant role of the IL7R gene in ovarian carcinoma. It is envisaged that the work will lay the foundation for the development of a novel biomarker with potential application in molecular profiling and in estimation of the disease prognosis.Communicated by Ramaswamy H. Sarma.