Somatic mutation analyses of stem-like cells in gingivobuccal oral squamous cell carcinoma reveals DNA damage response genes.

Gingivobuccal oral squamous cell carcinoma (OSCC-GB) occurs among persons who excessively chew smokeless tobacco in India. To understand the role of cancer stem cells (CSCs) in the disease, we have performed transcriptomics analysis on RNA-seq data from OSCC-GB primary tumors. The mutational signature analysis of the identified novel and Catalogue of Somatic Mutations in Cancer (COSMIC) variants reveals DNA damage associated etiology based on identified COSMIC signatures showing a higher prevalence of C > T mutations and 1 bp T/(A) nucleotide insertions, pointing to the role of smokeless tobacco carcinogens. The differential somatic mutational, functional impact predictions, and survival analysis reveals the role of DNA damage response-related genes, with the CREBBP gene as a major player. The new CSC somatic variants identified in the study may play a crucial role in cancer metastasis, local-regional recurrence, chemo- and/or radioresistance that contributes to high mortality of the Indian OSCC-GB patients.