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Article Abstract

Metastatic colorectal cancer (mCRC) presents notable therapeutic challenges. Rat sarcoma virus () mutations, including those in exon 2, are critical for treatment decisions; however, the role of minor mutations ( exons 3 and 4, and ) remains underexplored. Because these mutations are increasingly identified in routine practice due to advances in mutation testing that now routinely includes exons 3 and 4, and , clarifying their clinical relevance has become important for ensuring appropriate treatment selection. The present study aimed to compare the clinical and prognostic characteristics of patients with mCRC with minor mutations to those with exon 2 mutations. To this end, data were retrospectively collected from patients with mCRC and mutations between August 2018 and December 2023. Patients were grouped based on mutation subtype: exon 2 or minor mutations. mutation testing was performed using the MEBGEN RASKET™-B kit. Clinical characteristics, tumor location, metastatic patterns and survival outcomes were analyzed. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier survival analysis, log-rank tests and Cox proportional hazards regression models. Of 202 patients with mutations, 170 had exon 2 mutations, whereas 32 exhibited minor mutations (20 with non-exon 2 mutations and 12 with mutations). Minor mutations were more common in left-sided CRC. No significant differences in background were observed between the two groups. Log-rank OS was comparable for patients with exon 2 and minor mutations. OS and PFS with first-line bevacizumab-containing therapy were also similar between the two groups. In conclusion, the prognostic impact of minor mutations appears to be comparable to that of exon 2 mutations, suggesting that the current treatment strategies for -mutant CRC may not require modification based on these findings.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150841PMC
http://dx.doi.org/10.3892/ol.2025.15123DOI Listing

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