Genetic profiling of metastatic colon adenocarcinoma in Iranian patients: Insights into pathogenic variants and tumor characteristics

Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality, and understanding the genetic landscape is crucial for improving targeted therapies. This study aimed to analyze the tumor's genetic profiles of patients with metastatic CRC, focusing on pathogenic or likely pathogenic variants in tumor related genes.

The present cross-sectional study was conducted on 40 Persian patients with metastatic colorectal adenocarcinoma. Formalin-fixed paraffin-embedded tumor samples were analyzed using next generation sequencing technique to detect pathogenic variants. The patients' tumor characteristics, including differentiation grades and tumor sites (colon, rectum, or rectosigmoid), were documented and the relationship between variants and tumor characteristics was evaluated.

The study population had a mean age of 55.75 ± 12.88 years, and 60 % were female. The most common tumor site was the colon (52.5 %), followed by rectosigmoid (27.5 %) and cecum (20 %). APC gene variants were prevalent in 72.5 % of patients, with the p.Arg876* variant being the most frequent. TP53 gene variants were present in 65 %, with p.Trp146* and p.Arg273His being the most common. Pathogenic KRAS gene variants were observed in 50 %, significantly associated with rectosigmoid involvement (p = 0.001). The ERBB2 CNVs were found in 25 % of patients and were associated with colon involvement (p = 0.021).

The study highlights the genetic diversity in Persian patients with metastatic colon adenocarcinoma and demonstrated that APC and TP53 variants were the most prevalent, while KRAS and ERBB2 variants were associated with specific tumor sites. These findings provide a basis for personalized treatment strategies in CRC among Persian population.