Genomic landscape of pathogenic mutations in Pakistani population with late-stage colorectal cancer.

Objective: To assess the frequencies of pathogenic mutations in Pakistani population with late-stage Colorectal cancer (CRC).

Methods: This was a descriptive analysis of CRC patients who got their next-generation sequencing (NGS) tests (targeted panel) done at AKUH, Karachi between January 2021 and December 2021. Pathogenic variants were identified using American College of Medical Genetics and Genomics (ACMG) classification.

Results: Among the 35 CRC patients analyzed, 31.4% were < 50 years old and 60% were males. Mutation analysis showed a high prevalence of TP53 mutations in 23 patients (65.7%). KRAS mutations were detected in 19 patients (54.3%) Other mutations included PIK3CA in 3(8.6%), NRAS in 3(8.6%), EGFR in 3(8.6%), and MET in 1(2.9%). Double gene mutation (KRAS and TP53) were observed in 13 (37.1%) and (PIK3CA and KRAS) in 2 (5.71%) samples. A triple gene mutations (KRAS, TP53, and PIK3CA) were found in 1 (3%) of CRC tumors. The remaining samples were wild type for genes analyzed. Microsatellite instability (MSI) status was assessed, revealing 2.9% MSI-high tumors, 37.1% MSI-stable tumors, and a concerningly high proportion (60.0%) of samples where MSI testing was not performed.

Conclusion: This study highlights distinct a genetic profile of CRC in the Pakistani population, characterized by a significant prevalence of TP53 and KRAS mutations.