Frequency of RAS family gene mutations in metastatic solid tumors in Venezuela: Experience at a large academic center.

Abstract

e13538 Background: Understanding the molecular profile of cancer-associated genes is crucial in oncology, as it informs targeted therapies and improves patient outcomes. Tumor suppressor genes inhibit the activation of oncogenic signals, while oncogenes promote them. Ras proteins, encoded by KRAS, NRAS, and HRAS genes, are involved in cell growth, differentiation, and survival pathways. This study aims to investigate the frequency of KRAS, NRAS, and HRAS mutations in solid tumors treated at a single academic institution between January 2017 and May 2024. By analyzing these mutations, we seek to enhance our understanding of their distribution across different cancer types in Venezuela, providing valuable insights for personalized cancer treatment strategies. Methods: We conducted a retrospective, cross-sectional, analytical cohort study. The study included 175 patients, with 179 molecular genetic sequencing studies and 20 RT-PCR analyses. We examined mutations in codons 12, 13, 59, 61, 117, and 146 of the KRAS, NRAS, and HRAS genes. Results: We identified 43 mutations in the RAS gene family: 37 in KRAS, 5 in NRAS, and 1 in HRAS. Lung cancer accounted for 14 of those mutations, with 13 in KRAS and 1 in HRAS. Colorectal cancer showed 19 mutations, with 16 in KRAS and 3 in NRAS. Other KRAS mutations (13.9%) were found in breast, endometrial, pancreatic cancers, and thymoma. We also recorded 2 NRAS mutations in melanoma and 1 in pancreatic cancer. Conclusions: This study represents the largest collection of KRAS, NRAS, and HRAS mutations reported in Venezuela.