Background: Gallbladder cancer (GBC) has a peculiar geographical distinction, with a high prevalence seen in North India and Chile. There are various aetiopathogenetic mechanisms of GBC causation; one of them is a series of pathogenic mutations, which is responsible for the malignant transformation of gallbladder epithelium. Therefore, the present study aimed to find out cancer-specific hot spot mutations in five major cancer-related genes KRAS exon1 &2, NRAS exon1, IDH2 exon, PIK3CA exon 20, IDH2 exon 4 and EGFR exon 20 in North Indian GBC patients and their association with clinicopathological variables.

Material and methods: This study included 34 histopathologically confirmed GBC cases. The clinical material consisted of formalin-fixed paraffin-embedded (FFPE) blocks of the patients. DNA isolation was done from FFPE tissue. DNA sequencing was performed by the capillary electrophoresis method. The chi-square (χ2) test was used to test for a statistically significant relationship between two categorical study variables.

Results: The overall incidence of somatic mutations in KRAS exon 1&2, NRAS exon1, IDH2 exon4, PIK3CA exon20, and EGFR exon 20 in Indian GBC patients was found in 8/34 (23.5%), 3/34 (8.8%), 4/34 (11.7%), 7/34 (20.6%), 7/34 (20.6%), respectively. KRAS exon 1 and two mutations were found to be significantly associated with advanced stage GBC patients.

Conclusion: KRAS, PIK3CA, and EGFR were found to be the most frequently mutated genes among the five tested in this study.