Test Catalog

Test ID: BRAFB    
Cell-Free DNA BRAF V600 Test, Blood

Useful For Suggests clinical disorders or settings where the test may be helpful

An alternative to invasive tissue biopsies for the determination of BRAF V600E and V600 K mutations

 

Identification of patients with melanoma who are most likely to benefit from targeted therapies

Genetics Test Information Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test evaluates cell-free DNA (cfDNA) in the peripheral blood for the presence of BRAF V600E or K mutations in patients with melanoma and can be used to determine if these patients are candidates for targeted therapies.

 

This test is not validated for serial monitoring of patients with malignant melanoma, nor should it be used for evaluating patients with other malignancies. This test is also not intended as a screening test to identify cancer.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

This test uses DNA extracted from the peripheral blood to evaluate for the presence of BRAF V600E and V600K mutations. A positive result indicates the presence of an activating BRAF mutation and may be useful for guiding the treatment of individuals with melanoma.

 

Targeted cancer therapies are defined as antibody or small molecule drugs that block the growth and spread of cancer by interfering with specific cell molecules involved in tumor growth and progression. Multiple targeted therapies have been approved by the FDA for treatment of specific cancers. Molecular genetic profiling is often needed to identify targets amenable to targeted therapies and to minimize treatment costs and therapy-associated risks.

Interpretation Provides information to assist in interpretation of the test results

An interpretive report will be provided.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Patients with a negative test result may still harbor a V600E or V600K mutation. Mutation testing of a tissue specimen for BRAF mutations should be considered for patients with a negative result with this test.

 

The limit of detection of this assay for the detection of BRAF V600E and V600K mutations is influenced by the amount of cfDNA in the blood. This is a biological variable that cannot be controlled.

 

This assay was designed to detect V600E and K mutations. The sensitivity for rarer V600 mutations has not been established.

 

This test has not been clinically validated for use as a tool to monitor response to therapy or for early detection of tumors.

 

This test cannot differentiate between somatic and germline alterations.

Supportive Data

This test has been evaluated by our laboratory as an alternative to assessing paraffin embedded tumor specimens for BRAF mutations in patients with advanced melanoma. Those studies revealed that this assay has a high positive predictive value (100% in our study) for the presence of a BRAF V600 mutation in a patient’s tumor and high concordance between the specific mutation type observed in the patient’s plasma and tumor.

 

While the positive predictive value of this assay was very high, the negative predictive value of the assay in this study (using BRAF tissue result as the gold standard) was only 71%.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Sanmamed MJ, Fernandez-Landazuri S, Rodriguez C, et al: Quantitative cell-free circulating BRAFV600E mutation analysis by use of droplet digital PCR in the follow-up of patients with melanoma being treated with BRAF inhibitors. Clin Chem 2015;61(1):297-304

2. Schwarzenbach H, Hoon DS, Pantel K: Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer 2011;11(6):426-437

3. Johnson DB, Sosman JA: Update on the targeted therapy of melanoma. Curr Treat Options Oncol 2013;(2):280-292

4. McArthur GA, Chapman PB, Robert C, et al: Safety and efficacy of vemurafenib in BRAF (V600E) and BRAF (V600K) mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomized, open-label study. Lancet Oncol 2014 Mar;15(3):323-332