Genomic profiling of lung adenocarcinoma and squamous carcinoma in Indian patients: Implications for precision oncology.

Abstract

e20599 Background: Lung cancer, the leading cause of cancer related mortalities, remains a significant global health burden. Despite advances in next generation sequencing technologies, the genomic landscape of non-small cell lung cancer (NSCLC) in the Indian patients remains underexplored. In this study, we aimed to elucidate the genomic landscape of lung adenocarcinoma and squamous carcinoma among Indian patients using targeted sequencing data of over 400 lung cancer patients. Methods: Utilizing targeted sequencing of 50 established cancer-related genes, we conducted a comprehensive analysis of the genomic alteration profiles in 325 lung adenocarcinoma and 81 lung squamous carcinoma samples from Indian patients. Further, we employed robust statistical methodologies to delineate correlations between genomic alterations and clinical characteristics including age, gender, extent of disease, habits and PD-L1 status. Furthermore, our investigation revealed distinctive genomic signatures of NSCLC specific to the Indian population through comparative analyses across various ethnicities. Results: EGFR mutations were detected in 45.8% of lung adenocarcinoma and a notable 18% of lung squamous carcinoma cases among Indian patients, showing significant prevalence among females and non-smokers. Alongside EGFR, lung adenocarcinoma patients exhibited frequent alterations in TP53 (27.4%), ALK (11.4%), and KRAS (10.2%), while lung squamous carcinoma cases predominantly showed mutations in TP53 (40.7%), PIK3CA (17.3%), and CDKN2A (8.6%). Remarkably, 68% of lung adenocarcinoma cases deemed eligible for NCCN-approved targeted therapies. Additionally, it was observed that 60% of PD-L1-negative squamous carcinoma patients harbored TP53 alterations, indicating intriguing therapeutic implications. Overall, we observed alterations in 88% lung adenocarcinoma and 70% lung squamous carcinoma patients. Conclusions: Our study unveiled distinct genomic variations present in both adenocarcinoma and squamous carcinoma patients from India, revealing crucial insights for precision medicine and clinical management of lung cancer. Our findings provide a significant lead for designing clinical trials aimed at evaluating EGFR inhibitors in lung squamous carcinoma patients, potentially expanding therapeutic options for Indian lung cancer patients.