Whole exome sequencing of oral tumours from female patients from southern Indian cohort

Whole exome sequencing of oral tumours from female patients from southern Indian cohort Oral squamous cell carcinoma (OSCC) is one of the frequently diagnosed cancer types in both male and females in India due to rampant tobacco chewing. As the prevalence of OSCC among men is a bit higher, there is an over enrichment of male patients in previous genomic studies performed by our and other groups. Thus we undertook a study where we recruited female OSCC patients from a southern Indian cohort where prevalence of OSCC among females is also high. Analyses of whole exome sequence data from 38 OSCC patients from this cohort, we have identified 10 significantly mutated genes including TP53, CDKN2A, HLA-B, CASP8 and copy number amplification including EGFR and deletions including CDKN2A, which were also previously implicated in oral cancer; although the frequency of mutation in some of these genes significantly differ from other Indian OSCC cohorts as well as TCGA head and neck cancer cohort. The most frequently mutated driver gene was found to be CASP8 in this cohort followed by TP53. We found TP53 mutation was associated with higher tumour heterogeneity and shorter disease-free survival of the patients. Somatic mutations in pathways including Notch and PI3K-Akt signalling were significantly enriched in this cohort. We also found oncogenic mutations in TP53, PIK3CA and HRAS genes in these patients. Our further integration of histopathology data showed correlations of tumour immune infiltrations with specific somatic alterations which might have therapeutic implications.