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Abstract
Introduction. Brain metastases from colorectal cancer (CRC) are relatively rare but are associated with a poor prognosis. The rarity of this event complicates the study of the biological underpinnings of such a unique metastatic pattern.
Aim. To describe the molecular genetic characteristics of colorectal adenocarcinomas in patients with brain metastases.
Materials and Methods. Between 2006 and 2025, 200 patients with brain metastases from CRC were identified at the N.N. Blokhin National Medical Research Center of Oncology. This translational analysis included 71 patients for whom archived histological material from the primary colorectal tumor was available. The mutational status of KRAS, NRAS, and BRAF was assessed, and microsatellite instability (MSI) status was analyzed.
Results. Mutations in RAS family genes were identified in 38 out of 71 patients (53.5 %). Among these, pathogenic variants KRAS G12D (26.3 %) and G12V (23.7 %) predominated. The BRAF V600E mutation was detected in 8 patients (11.3 %), MSI was found in 5 patients (7.0 %). Notably, in 2 cases (2.8 %), the BRAF V600E mutation was identified concurrently with MSI.
Conclusion. Primary colorectal tumors in patients with brain metastases are characterized by a distinct molecular profile with a high frequency of mutations in RAS and BRAF genes, indicating a key pathogenetic role of the RAS/RAF/MAPK signaling pathway activation.
References
Wu S., Zhang Y., Lin Z., et al. Global burden of colorectal cancer in 2022 and projections to 2050: incidence and mortality estimates from GLOBOCAN. BMC Cancer. 2025; 25: 1770.-DOI: 10.1186/s12885-025-15138-0.
Ilyas M.I.M. Epidemiology of Stage IV Colorectal Cancer: Trends in the Incidence, Prevalence, Age Distribution, and Impact on Life Span. Clin Colon Rectal Surg. 2023; 37(2): 57-61.-DOI: 10.1055/s-0043-1761447.
Alfonzo Horowitz M., Li M., Parker M., et al. Incidence, demographics, and survival of patients with brain metastases from stage IV colorectal cancer: a population-based study from 2013 to 2023. J Neurooncol. 2025; 175: 123-131.-DOI: 10.1007/s11060-025-05107-9.
Sundermeyer M.L., Meropol N.J., Rogatko A., et al. Changing patterns of bone and brain metastases in patients with colorectal cancer. Clin Colorectal Cancer. 2005; 5(2): 108-113.-DOI: 10.3816/ccc.2005.n.022.
Christensen T.D., Spindler K.L.G., Palshof J.A., et al. Systematic review: brain metastases from colorectal cancer — Incidence and patient characteristics. BMC Cancer. 2016; 16: 260.-DOI: 10.1186/s12885-016-2290-5.
Ilic I., Ilic M. International patterns and trends in the brain cancer incidence and mortality: An observational study based on the global burden of disease. Heliyon. 2023; 9(7): e18222.-DOI: 10.1016/j.heliyon.2023.e18222.
Zeineddine F.A., Zeineddine M.A., Yousef A., et al. Survival improvement for patients with metastatic colorectal cancer over twenty years. npj Precis Onc. 2023; 7: 16.-DOI: 10.1038/s41698-023-00353-4.
Bonadio R.C., Freitas G.F., Batista D.N., et al. Epidemiology and outcomes of patients with brain metastases from colorectal cancer-who are these patients? Clin Colorectal Cancer. 2021; 20(3): e195-e200.-DOI: 10.1016/j.clcc.2021.04.002.
Roussille P., Auvray M., Vansteene D., et al. Prognostic factors of colorectal cancer patients with brain metastases. Radiother Oncol. 2021; 158: 67-73.-DOI: 10.1016/j.radonc.2021.02.006.
Sathe A., Zhang M., Bai X., et al. Colorectal cancer relies on an immunosuppressive cellular topography and genomic adaptations for establishing brain metastases. bioRxiv [Preprint]. 2025.-DOI: 10.1101/2025.11.14.688538.
Golas M.M., Gunawan B., Gutenberg A., et al. Cytogenetic signatures favoring metastatic organotropism in colorectal cancer. Nat Commun. 2025; 16: 3261.-DOI: 10.1038/s41467-025-58413-1.
Michl M., Taverna F., Woischke C., et al. Identification of a gene expression signature associated with brain metastasis in colorectal cancer. Clin Transl Oncol. 2024; 26: 1886-1895.-DOI: 10.1007/s12094-024-03408-5.
Fort D.G., Herr T.M., Shaw P.L., et al. Mapping the evolving definitions of translational research. J Clin Transl Sci. 2017; 1(1): 60-66.-DOI: 10.1017/cts.2016.10.
Bylsma L., Gillezeau C., Garawin T., et al. Prevalence of RAS and BRAF mutations in metastatic colorectal cancer patients by tumor sidedness: A systematic review and meta‐analysis. Cancer Med. 2020; 9: 1044-1057.-DOI: 10.1002/cam4.2747.
Ciepiela I., Szczepaniak M., Ciepiela P., et al. Tumor location matters, next generation sequencing mutation profiling of left-sided, rectal, and right-sided colorectal tumors in 552 patients. Sci Rep. 2024; 14.-DOI: 10.1038/s41598-024-55139-w.
Martianov A.S., Mitiushkina N.V., Ershova A.N., et al. KRAS, NRAS, BRAF, HER2 and MSI status in a large consecutive series of colorectal carcinomas. Int J Mol Sci. 2023; 24: 4868.-DOI: 10.3390/ijms24054868.
De Souza Barbosa I., Heming C., Neto V., Aran V. The role of RAS in CNS tumors: A key player or an overlooked oncogene? Int J Mol Sci. 2025; 26.-DOI: 10.3390/ijms26094104.
Bahar M., Kim H., Kim D. Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies. Signal Transduct Target Ther. 2023; 8.-DOI: 10.1038/s41392-023-01705-z.
Baran B., Ozupek N., Tetik N., et al. Difference between left-sided and right-sided colorectal cancer: A focused review of literature. Gastroenterology Res. 2018; 11: 264-273.-DOI: 10.14740/gr1062w.
Pino M., Chung D. The chromosomal instability pathway in colon cancer. Gastroenterology. 2010; 138(6): 2059-2072.-DOI: 10.1053/j.gastro.2009.12.065.
Cejas P., López-Gomez M., Aguayo C., et al. KRAS mutations in primary colorectal cancer tumors and related metastases: a potential role in prediction of lung metastasis. PLoS One. 2009; 4(12): e8199.-DOI: 10.1371/journal.pone.0008199.
Franceschi W., Bliggenstorfer J., Sarode A.L., et al. Primary colorectal tumor location and predictors for metastasis to the brain. Cureus. 2023; 15(5): e39735.-DOI: 10.7759/cureus.39735.
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