Genomic landscape of oral squamous cell carcinoma from the southwest coast of Karnataka: insights from FFPE-based next-generation sequencing

TL;DR

This study uses genomic sequencing to analyze oral cancer in a specific Indian region, finding key mutations and suggesting personalized treatment approaches.

Contribution

The study provides region-specific genomic insights into oral squamous cell carcinoma using FFPE-based sequencing and identifies potential clinical implications.

Findings

A core set of 21 genes showed pathogenic or drug-response variants in all patients.

15 of 21 patients had the highest polygenic risk scores, indicating strong inherited susceptibility.

Pathway analysis revealed enrichment in p53 signaling, immune pathways, and platinum-drug resistance.

Abstract

Oral squamous cell carcinoma (OSCC) remains a major health burden in India, yet region-specific genomic data are limited. This study aimed to characterize the mutational landscape of OSCC patients from the southwest coast of Karnataka using FFPE tissues and assess potential clinical correlations.

Whole-exome sequencing was performed on tumor and adjacent normal FFPE samples from 21 OSCC patients. Variants were annotated using multiple clinical databases, and stratified analyses were conducted across clinicopathological parameters including age, sex, tumor site, and TNM stage.

We identified extensive inter-patient variability in clinically relevant mutations, with intronic and missense variants being most frequent. A core set of 21 genes including ABCB1, CD44, IL6, PADI2, and VKORC1—carried pathogenic or drug-response variants in all patients. Ten tumor-exclusive mutations were observed, including TLR1 rs5743618, present in 100% of tumors. Pathway and network analyses highlighted enrichment in p53 signaling, immune pathways, and platinum-drug resistance. Stratified analyses showed no significant differences in mutation burden across TNM stages (Kruskal–Wallis p = 0.952), nodal status (p = 0.460), age, or sex. Polygenic risk score estimation revealed that 15 of 21 patients belonged to the highest-risk quartile, suggesting strong inherited susceptibility.

FFPE-based genomic profiling successfully captured key OSCC-associated alterations and revealed region-specific mutation signatures. The predominance of germline and pharmacogenomic variants and strong PRS enrichment underscore the potential of incorporating hereditary risk assessment and targeted therapy selection into OSCC management strategies in this population.

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