BRAF V600E, K, & D Mutations: Identify
10-15% More Patients Who May Respond to Vemurafenib

Our BRAF V600E/K/D Mutation Test is a highly sensitive, extensively validated lab-developed test that identifies up to 65% of melanomas as potentially responsive to BRAF-inhibitor therapy.

Melanoma treatment advanced significantly in August 2011 with the FDA’s approval of ZELBORAF® (vemurafenib) for patients with metastatic or inoperable tumors that carry the BRAF-activating V600E mutation. Patients carrying the V600K mutation have also shown response to vemurafenib, and pre-clinical evidence demonstrates effect against the V600D mutation. NeoGenomics provides high-sensitivity, rapid diagnostic testing in paraffin-embedded melanoma tumors for all three activating mutations to identify more patients for whom vemurafenib therapy can be considered.

Testing for BRAF V600K and V600D mutations identifies another 10-15% of melanomas as potentially responsive to drug therapy. V600E occurs in ~50% of melanomas.
Assay sensitivity of ≥1% abnormal DNA surpasses other commercially-available tests and improves mutation detection in samples with low tumor burden.
Specific detection and differentiation of the three mutations allows better estimate of likelihood of drug response.

Test Details

Assay description: Allele-specific real-time PCR provides qualitative detection of the V600E (c.1799T>A), V600K, and V600D mutations by selective amplification of mutant alleles.
Sensitivity: This PCR-based assay is designed to detect 1% or more mutant DNA in a background of wildtype DNA.
Specimen requirements: Formalin-fixed paraffin embedded block. Preferred tumor size in block is 3x3 mm or more.
TAT: 7 days
CPT codes: 83891x1, 83896x3, 83898x3, 83907x1, 83912x1.

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Download the Test Guide (PDF)

Companion Diagnostic Policy

In the unlikely event Zelboraf® coverage or prior authorization for coverage is denied for a V600E-positive patient because of the lab-developed nature of the test, NeoGenomics will immediately refer the positive case to a partner laboratory for re-analysis with an FDA-approved test. NeoGenomics will cover any additional costs associated with this testing. Negative cases and V600K or V600D-positive cases will be reported and not be sent for further testing.

NCCN Guidelines support either FDA-approved testing or testing in a CLIA-approved facility. NeoGenomics has full CLIA accreditation.

Supporting Research

Drug approval was largely due to the success of the BRIM-2 and BRIM-3 trials which showed vemurafenib to be the first individual drug to improve response rates, progression-free survival (PFS), and overall survival (OS) compared to standard BRAF Mutation Pathway chemotherapy. Patients in both studies tested positive for BRAF V600 mutations and had metastatic or unresectable melanoma. Approximately half of patients responded to vemurafenib. Some were later shown to carry the V600K mutation instead of the V600E mutation. These patients showed a range of response from none to excellent, and in the major study, 4/10 showed partial response. Data about clinical response in V600D-positive melanomas is not yet available. However, in vitro studies show BRAF pathway-specific inhibition of proliferation in V600D cell lines and suggest clinical sensitivity.

BRAF is a kinase member of the RAS-RAF-MAPK signaling pathway that promotes cell proliferation and survival. Activating mutations lead to constitutive activation of the pathway, resulting in abnormal cell growth. Vemurafenib inhibits multiple kinases, but its most potent effects in inhibiting ERK phosphorylation and blocking cell proliferation are specific to BRAF V600-mutated cells.