Integrative study of whole exome variation and expression in gingivo-buccal oral squamous cell carcinoma revealed alteration in TLR-activated MAP-Kinase signalling

Oral cancer remains a major concern with high incidence and mortality despite multiple genomic and transcriptomic studies. In this study, integrating the genomic and transcriptomic profiles, we tried to put forward any undescribed drivers which may be prospective therapeutic targets. Whole Exome sequencing was performed from oral carcinoma and paired normal or blood tissues from 11 Indian patients and mutation data were validated in another set of tumor tissues from 27 Indian patients. The results were integrated with our published transcriptome sequencing data from same 11 patients. Validation of imbalance in allelic expression of TP53 (p.E154K) and expression of IL8 were performed by qPCR in another set of 41 Indian samples. The results highlighted CUX1 as an important driver, not reported much in oral cancer. MAPK signalling activated by toll-like receptors and interleukins was also observed to be one of the enriched deregulated pathways with its genes as future druggable targets in oral cancer. Imbalance in allelic expression in tumor highlighted gain-of-function variants of KRAS along with TP53 as an important phenomenon in oral cancer. The study presents important drivers of oral cancer along with most altered pathway. Imbalance in allelic expression has been uncovered to focus on relevant genes which might have translational potential.