ORIGINAL RESEARCH article
Front. Oncol.
Sec. Gastrointestinal Cancers: Colorectal Cancer
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1621412
This article is part of the Research TopicExploring Molecular Mechanisms in Cancer through Tumor Molecular PathologyView all 9 articles
A compilation of 13 patients with metastatic colorectal cancer and concomitant BRAF and RAS family mutations
Provisionally accepted
- 1Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, United States
- 2Department of Biostatistics and Data Science, Wake Forest University School of Medicine, Winston-Salem, NC, United States
- 3Department of Hematology & Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, United States
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Metastatic colorectal cancer (mCRC) exhibits significant heterogeneity in molecular profiles, influencing treatment response and patient outcomes. Mutations in v-raf murine sarcoma viral oncogene homolog B1 (BRAF) and rat sarcoma (RAS) family genes are commonly observed in mCRC. Though originally thought to be mutually exclusive, recent data have shown that patients may present with concomitant RAS and BRAF mutations, posing unique challenges and implications for clinical management. Below we present a retrospective study on 13 patients with concomitant BRAF and RAS (KRAS, NRAS) mutations in mCRC and describe their clinical features and treatment outcomes. We reviewed over 750 samples from a database of CRC patients from Guardant360 and FoundationOne kept by the Wake Forest Baptist Health Comprehensive Cancer Center. The study population included patients greater than the age of 18 who were diagnosed with mCRC harboring both BRAF and RAS mutations, as identified by next generation sequencing. Thirteen mCRC patients, 61.5% male, with a median age of diagnosis of 64.4 years had concomitant BRAF and RAS mutation. 61.5% of patients had right-sided primary disease. 61.5% patients had mutations in codon 12 of KRAS, 15.4% had BRAF G466V, and 15.4% had BRAF V600E mutations. 69.2% patients had liver metastasis, 23.1% had peritoneal metastases and 7.7% suffered metastasis to supraclavicular, retroperitoneal, and mesenteric lymph nodes. Median time from diagnosis of stage IV disease to progression was 25.3 months and median overall survival was 4.9 years. This study adds more insight to the limited existing data regarding rare mCRC cases with concomitant BRAF and RAS family mutations and exposes the need for future research on larger populations of this rare subset of patients.
Keywords: colorectal cancer, BRAF mutation, RAS mutation, concurrent RAS/BRAF variants, clinical-pathological features
Received: 01 May 2025; Accepted: 06 Aug 2025.
Copyright: © 2025 Srivastav, Lehman, Evans, Paluri and Rocha Lima. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Morgan E Lehman, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, United States
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