Distinct genomic landscape of non-small cell lung cancer in Bangladeshi patients: Implications for precision oncology in a resource-limited setting

BACKGROUND: Non-small cell lung cancer (NSCLC) is a genetically heterogeneous disease with clinically actionable mutations. Analysis of circulating tumor DNA (ctDNA) in plasma using next-generation sequencing (NGS) provides a minimally invasive method for profiling tumor-associated genomic alterations. However, the ctDNA mutational landscapes of Bangladeshi NSCLC patients remain scarce. METHODS: We enrolled 106 patients with NSCLC and performed targeted NGS of ctDNA, covering a panel of key genes, including EGFR, TP53, KRAS, ERBB2, BRAF, MET, NRAS, PIK3CA, ALK,MAP2K1, and ROS1. RESULTS: Mutations were detected in 85.8% of patients, with TP53, EGFR, and KRAS being the most frequently altered genes. Single gene mutations predominated in females, whereas males exhibited higher rates of multiple concurrent mutations, and KRAS mutations were significantly associated with males. Pathogenic variant c.2155G>A of EGFR was most frequent in the 50-70-year group. The TP53 pathogenic variant c.580G>A was found in 14 patients, and 11 patients showed pathogenic variant c.35G>A in KRAS. The highest number of pathogenic mutations was found in EGFR, followed by TP53, KRAS, ERBB2, BRAF, NRAS, MET, and PIK3CA. No mutation was found in ROS1. Prevalence of EGFR mutations aligns with that in other Asian populations, while frequencies of TP53 and KRAS mutations are consistent with global datasets. CONCLUSION: The high prevalence of EGFR and TP53 alterations underscores the importance of molecular testing to guide targeted therapy. This is the first comprehensive ctDNA-based genomic landscape for NSCLC in Bangladesh and supports the integration of liquid biopsy into precision oncology strategies in resource-limited settings.