KRAS and BRAF Mutation Analysis

KRAS and BRAF are prone to mutations in sporadic colorectal carcinomas (CRC).
BRAF is a downstream molecule from KRAS in a signaling pathway involved in cell cycling.

KRAS mutations can be detected in approximately 30-40% of all patients with colon cancer.
BRAF mutations are responsible for an additional 12-15% of patients who fail to respond to anti-EGFR treatment.

KRAS and BRAF mutations are associated with shorter PFS and OS.
KRAS and BRAF mutations correlate with lack of response to treatment with anti-EGFR therapies.
Patients with wild-type KRAS and BRAF have shown much greater benefi t to anti-EGFR therapies.

KRAS and BRAF mutations are detected using polymerase chain reaction on DNA from tumor sections.
Majority of mutations are reported on codons 12 and 13 for KRAS and codon V600E for BRAF.
Testing for the BRAF V600E mutation compliments KRAS mutation analysis and may be as important as KRAS testing for treatment decisions.
Testing avoids unnecessary toxicity, treatment delays and monetary cost to patients who may not respond to anti-EGFR therapies.
Testing for BRAF and KRAS status could be useful in identifying patients suitable for anti- EGFR therapy.
NCCN v.4.2008 guideline recommends KRAS testing in all metastatic colorectal cancer patients prior to initiating anti-EGFR therapy.
ASCO 2009 releases provisional clinical opinion that all patients with metastatic colorectal carcinoma who are candidates for anti-EGFR therapy should be tested for KRAS mutation.