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Clinical Characterization of Targetable Mutations (BRAF V600E and KRAS G12C) in Advanced Colorectal Cancer-A
Paweł M Potocki1, Piotr Wójcik2, Łukasz Chmura2
1Oncology Department, Faculty of Medicine, Jagiellonian University Medical College, 31-008 Cracow, Poland.
Abstract:
BRAF V600E and KRAS mutations that occur in colorectal cancer (CRC) define a subpopulation of patients with an inferior prognosis. Recently, the first BRAF V600E-targeting therapy has been approved and novel agents targeting KRAS G12C are being evaluated in CRC. A better understanding of the clinical characteristics of the populations defined by those mutations is needed. We created a retrospective database that collects clinical characteristics of patients with metastatic CRC evaluated for RAS and BRAF mutations in a single laboratory. A total of 7604 patients tested between October 2017 and December 2019 were included in the analysis. The prevalence of BRAF V600E was 6.77%. Female sex, primary in the right colon, high-grade, mucinous, signet cell, partially neuroendocrine histology, perineural and vascular invasion, and surgical tissue sample were factors associated with increased mutation rates. The prevalence of KRAS G12C was 3.11%. Cancer of primary origin in the left colon and in samples from brain metastases were associated with increased mutation rates. The high prevalence of the BRAF V600E mutation in cancers with a neuroendocrine component identifies a potential candidate population for BRAF inhibition. The association of KRAS G12C with the left part of the intestine and brain metastases of CRC are new findings and require further investigation.
Insights
BRAF V600E and KRAS mutations are common in colorectal cancer (CRC), impacting prognosis. Understanding their clinical features aids targeted therapy development for CRC patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- BRAF V600E and KRAS mutations are key drivers in colorectal cancer (CRC), associated with poorer patient outcomes.
- Targeted therapies for BRAF V600E and KRAS G12C mutations are emerging, necessitating a deeper understanding of associated clinical characteristics.
Purpose of the Study:
- To investigate the clinical features associated with BRAF V600E and KRAS G12C mutations in metastatic colorectal cancer.
- To identify patient subpopulations that may benefit from emerging targeted therapies.
Main Methods:
- Retrospective analysis of a database containing clinical characteristics of 7604 patients with metastatic CRC.
- Evaluation of RAS and BRAF mutations performed in a single laboratory between October 2017 and December 2019.
Main Results:
- BRAF V600E mutation prevalence was 6.77%, associated with female sex, right colon primary, high-grade histology, mucinous/signet cell components, neuroendocrine features, invasion, and surgical samples.
- KRAS G12C mutation prevalence was 3.11%, associated with left colon primary and brain metastases.
Conclusions:
- BRAF V600E mutations in neuroendocrine CRC highlight a potential population for BRAF inhibitors.
- KRAS G12C mutations in left-sided CRC and brain metastases are novel findings requiring further research for CRC treatment strategies.
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