A compilation of 13 patients with metastatic colorectal cancer and concomitant BRAF and RAS family mutations

IntroductionMetastatic 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 o...

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Main Authors: Jigisha Srivastav, Morgan E. Lehman, Joni K. Evans, Ravi Paluri, Caio Max Sao Pedro Rocha Lima
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Oncology
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Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2025.1621412/full
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author Jigisha Srivastav
Morgan E. Lehman
Joni K. Evans
Ravi Paluri
Caio Max Sao Pedro Rocha Lima
author_facet Jigisha Srivastav
Morgan E. Lehman
Joni K. Evans
Ravi Paluri
Caio Max Sao Pedro Rocha Lima
author_sort Jigisha Srivastav
collection DOAJ
description IntroductionMetastatic 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.MethodsBelow 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.ResultsThirteen 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.DiscussionThis 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.
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spelling doaj-art-fd7af83afb304a4bbbfe99b0be8ac0692025-08-25T04:10:31ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-08-011510.3389/fonc.2025.16214121621412A compilation of 13 patients with metastatic colorectal cancer and concomitant BRAF and RAS family mutationsJigisha Srivastav0Morgan E. Lehman1Joni K. Evans2Ravi Paluri3Caio Max Sao Pedro Rocha Lima4Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, United StatesDepartment of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, United StatesDepartment of Biostatistics and Data Science, Wake Forest University School of Medicine, Winston-Salem, NC, United StatesDepartment of Hematology and Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, United StatesDepartment of Hematology and Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, United StatesIntroductionMetastatic 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.MethodsBelow 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.ResultsThirteen 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.DiscussionThis 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.https://www.frontiersin.org/articles/10.3389/fonc.2025.1621412/fullcolorectal cancerBRAF mutationKRAS mutationNRAS mutationRAS family mutationconcurrent RAS/BRAF variants
spellingShingle Jigisha Srivastav
Morgan E. Lehman
Joni K. Evans
Ravi Paluri
Caio Max Sao Pedro Rocha Lima
A compilation of 13 patients with metastatic colorectal cancer and concomitant BRAF and RAS family mutations
Frontiers in Oncology
colorectal cancer
BRAF mutation
KRAS mutation
NRAS mutation
RAS family mutation
concurrent RAS/BRAF variants
title A compilation of 13 patients with metastatic colorectal cancer and concomitant BRAF and RAS family mutations
title_full A compilation of 13 patients with metastatic colorectal cancer and concomitant BRAF and RAS family mutations
title_fullStr A compilation of 13 patients with metastatic colorectal cancer and concomitant BRAF and RAS family mutations
title_full_unstemmed A compilation of 13 patients with metastatic colorectal cancer and concomitant BRAF and RAS family mutations
title_short A compilation of 13 patients with metastatic colorectal cancer and concomitant BRAF and RAS family mutations
title_sort compilation of 13 patients with metastatic colorectal cancer and concomitant braf and ras family mutations
topic colorectal cancer
BRAF mutation
KRAS mutation
NRAS mutation
RAS family mutation
concurrent RAS/BRAF variants
url https://www.frontiersin.org/articles/10.3389/fonc.2025.1621412/full
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