Sorted By Test Name - Mayo Medical Laboratories

BRAFM
83837
BRAF
87980
tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising
from papillary carcinomas. J Clin Endocrinol Metab 2003;88:5399-5404
BRAF Mutation Analysis (V600), Melanoma
Clinical Information: Assessment for BRAF V600 mutations has clinical utility in that it is a
predictor of response to antimutant BRAF therapy. BRAF is a member of the mitogen-activated
protein/extracellular signal-regulated (MAP/ERK) kinase pathway, which plays a role in cell proliferation
and differentiation. Dysregulation of this pathway is a key factor in tumor progression. Targeted therapies
directed to components of this pathway have demonstrated some success with increases both in
progression-free and overall survival in patients with certain tumors. Effectiveness of these therapies,
however, depends in part on the mutation status of the pathway components. Malignant melanoma, one of
the most aggressive forms of skin cancer, has a high frequency of BRAF mutations. Approximately 44%
to 70% of melanoma cases have a BRAF mutation, and of those, approximately 50% to 90% are the
V600E mutation. Current data suggest that the efficacy of BRAF-targeted therapies in melanoma is
confined to patients with tumors with activating BRAF mutations, such as V600E, which leads to
increased activation of the kinase pathway. While this test was designed to evaluate for the V600E
alteration, cross-reactivity with other alterations at the V600 codon have been described. At this time, this
test is approved specifically for melanoma tumors. Please refer to BRAF/87980 BRAF Mutation Analysis
(V600E), Tumor for BRAF testing in nonmelanoma tumors.
Useful For: Identification of melanoma tumors that may respond to BRAF-targeted therapies
Interpretation: An interpretative report will be provided.
Reference Values:
An interpretative report will be provided.
Clinical References: 1. Anderson S, Bloom KJ, Vallera DU, et al: Multisite analytic performance
studies of a real-time polymerase chain reaction assay for the detection of BRAF V600E mutations in
formalin-fixed paraffin-embedded tissue specimens of malignant melanoma. Arch Pathol Lab Med 2012
Feb;136:1-7 2. Chapman PB, Hauschild A, Robert C, et al: BRIM-3 Study Group. Improved survival with
vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011 Jun;364(26):2507-2516 3.
Package insert: Cobas 4800 V600 Mutation Test. Roche Molecular Systems, Inc., Branchburg, NJ;
February 2011 4. Dhomen N, Marais R: BRAF signaling and targeted therapies in melanoma. Hematol
Oncol Clin North Am 2009 Jun;23(3):529-545, ix 5. Flaherty KT, Puzanov I, Kim KB, et al: Inhibition of
mutated, activated BRAF in metastatic melanoma. N Engl J Med 2010 Aug;363(9):809-819
BRAF Mutation Analysis (V600E), Tumor
Clinical Information: Hereditary nonpolyposis colon cancer (HNPCC), also known as Lynch
syndrome, is an inherited cancer syndrome caused by a germline mutation in 1 of several genes involved
in DNA mismatch repair (MMR), including MLH1, MSH2, MSH6 and PMS2. There are several
laboratory-based strategies that help establish the diagnosis of HNPCC/Lynch syndrome, including testing
tumor tissue for the presence of microsatellite instability (MSI-H) and loss of protein expression for any 1
of the MMR proteins by immunohistochemistry (IHC). It is important to note, however, that the MSI-H
tumor phenotype is not restricted to inherited cancer cases; approximately 20% of sporadic colon cancers
are MSI-H. Thus, MSI-H does not distinguish between a somatic (sporadic) and a germline (inherited)
mutation, nor does it identify which gene is involved. Although IHC analysis is helpful in identifying the
responsible gene, it also does not distinguish between somatic and germline defects. Defective MMR in
sporadic colon cancer is most often due to an abnormality in MLH1, and the most common cause of gene
inactivation is promoter hypermethylation (epigenetic silencing). A specific mutation in the BRAF gene
(V600E) has been shown to be present in approximately 70% of tumors with hypermethylation of the
MLH1 promoter. Importantly, the V600E mutation has not been identified to date in cases with germline
MLH1 mutations. Thus, direct assessment of MLH1 promoter methylation status and testing for the
BRAF V600E mutation can be used to help distinguish between a germline mutation and
epigenetic/somatic inactivation of MLH1. Tumors that have the BRAF V600E mutation and demonstrate
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