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.

Automated summary

This study examines the role of cancer stem cells (CSCs) in gingivobuccal oral squamous cell carcinoma (OSCC-GB), a disease prevalent among smokeless tobacco chewers in India. Transcriptomics analysis reveals DNA damage associated with the disease, potentially caused by the carcinogens in smokeless tobacco. Furthermore, somatic variants in DNA damage response-related genes, particularly CREBBP, may contribute to metastasis, recurrence, and treatment resistance in Indian OSCC-GB patients.