The molecular-genetic profile of brain metastases from colorectal cancer

Abstract

Introduction . Brain metastases from colorectal cancer are a rare pattern of disease progression associated with an extremely poor prognosis. The genetic landscape of cerebral metastases remains largely unexplored, creating a significant gap in understanding the mechanisms of neurotropic metastasis and the selection of personalized treatment strategies. Aim . To describe the molecular genetic characteristics of brain metastases in patients with colorectal cancer. Materials and Methods . From 2006 to 2025, 200 patients with brain metastases from colorectal cancer were identified at the N. N. Blokhin National Medical Research Center of Oncology. This translational analysis included patients with a history of neurosurgical intervention and preserved access to archival histological material of brain metastases. Thus, a cohort of 53 patients was formed, in whom the mutational status of the KRAS, NRAS, and BRAF genes was assessed, along with an analysis of microsatellite instability status. Results. RAS family mutations were detected in 69.8 % of patients (37 / 53), of which 91.9 % were KRAS mutations. The most frequent KRAS variants were G12V (29.4 %) and G12D (20.6 %). BRAF V600E mutation was found in 11.3 % of cases (6 / 53), and microsatellite instability in 9.4 % (5 / 53). No statistically significant association was found between the mutational status of brain metastases and their location relative to the tentorium cerebelli, number, or volume. Conclusion . Our findings describe the mutation frequency in cerebral metastases of colorectal cancer in a representative Russian cohort and indicate the absence of a direct association between the studied markers and the clinico-morphological characteristics of intracranial lesions.