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Updated: Jul 1, 2025

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
Published on: July 17, 2019
Concurrent NRAS-BRAF variants in metastatic colorectal cancer: a Tunisian case report
Hayet Douik1,2, Ghada Sahraoui1,3, Mohamed Jemaà2,4
1Pathology Department, Salah Azaiz Institute.
Abstract:
Target therapy for metastatic colorectal cancer needs the determination of KRAS, NRAS, and BRAF mutation status to identify patients resistant to anti-EGFR treatment. RAS genes (KRAS/NRAS) are mutated in 40-60% of metastatic colorectal cancer and BRAF in 5-10%. The presence of a double mutation in RAS and BRAF is rare. Therefore, RAS and BRAF mutations were considered exclusive. Herein, we describe a novel concomitant NRAS/BRAF mutation identified in a series of 865 colorectal cancer patients.
Insights
Targeted therapy for metastatic colorectal cancer requires KRAS, NRAS, and BRAF mutation testing. This study identified a rare, concomitant NRAS/BRAF mutation, challenging previous assumptions of exclusivity in colorectal cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Targeted therapy for metastatic colorectal cancer (mCRC) relies on identifying mutations in KRAS, NRAS, and BRAF to predict resistance to anti-EGFR treatments.
- RAS gene mutations (KRAS/NRAS) occur in 40-60% of mCRC cases, while BRAF mutations are found in 5-10%.
Observation:
- Historically, double mutations in RAS and BRAF were considered exceedingly rare and thus mutually exclusive in colorectal cancer.
- This study investigated the mutation status of KRAS, NRAS, and BRAF in a cohort of 865 colorectal cancer patients.
Findings:
- A novel concomitant NRAS/BRAF mutation was identified in the studied series of colorectal cancer patients.
- This finding challenges the long-held assumption that RAS and BRAF mutations are exclusive in colorectal cancer.
Implications:
- The discovery of concomitant NRAS/BRAF mutations necessitates a re-evaluation of current diagnostic strategies for metastatic colorectal cancer.
- Accurate identification of these co-occurring mutations may refine patient selection for targeted therapies and improve treatment outcomes.
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