BRAF Mutation Analysis

What the laboratory says this test is for

The thyroid mutation panel assesses for all 8 of the most common mutations or rearrangements associated with thyroid neoplasia. The BRAF codon 600 mutation, and RET/PTC1 and RET/PTC3 rearrangements are highly associated with papillary thyroid cancer, the PAX8-PPAR{gamma} with follicular carcinomas and RAS mutations (in either HRAS, KRAS and NRAS) usually with follicular neoplasms. See test codes 90477 (BRAF), 90473 (RET/PTC), 90474 (PPAR/PAX8), and 90479 (RAS panel) for individual components. A thyroid cytology diagnosis code with reflex to molecular, as appropriate, is also available.

What the laboratory says this test is for

BRAF encodes a serine/threonine protein kinase downstream of the epidermal growth factor receptor (EGFR) and the RAS family of small G-proteins (KRAS, HRAS and NRAS) in the MAPK pathway. BRAF is mutated in a variety of human tumors, most frequently in melanoma and in papillary thyroid cancer. BRAF mutations are also found in lower frequency in colorectal cancer, non-small cell lung cancer (NSCLC), acute myeloid leukemia (AML), hairy cell leukemia, glioma, sarcomas, breast cancer, hepatoma and ovarian cancer.BRAF mutations are found clustered within the P-loop (exons 11&12) and activation domain (exon 15) of the kinase domain. A single glutamic acid for valine substitution at codon 600 (V600E) in exon 15 comprises approximately 90% of BRAF somatic mutations in cancer. In general, BRAF V600E mutations do not coexist with RAS mutations in the same tumor cells, suggesting that each of these genetic alterations is sufficient for activating downstream effectors that initiate or promote tumorigenesis.The BRAF V600E mutation is also associated with significantly poor prognosis and higher recurrent and persistent disease in patients with melanomas, colorectal carcinoma, and papillary thyroid cancers. In patients with metastatic colorectal cancer, the presence of the BRAF V600E mutation in tumors with wild-type KRAS is associated with resistance to EGFR inhibitor therapy. In contrast, in patients with metastatic melanoma, BRAF V600E mutation may predict for response to BRAF inhibitors. Therefore, BRAF mutation analysis may be used either as a standalone test for the selection of cancer patients who might benefit from BRAF inhibitor therapies, or as an additional tool (along with RAS mutation analysis) for the selection of metastatic colorectal cancer patients that might benefit from EGFR-targeted therapies.

What the laboratory says this test is for

This assay provides morphologic review along with appropriate molecular testing for diagnosis of thyroid samples obtained by fine needle aspirate (FNA). Any molecular testing required will be reflexed based on cytologic findings and a comprehensive assessment issued summarizing the overall findings. Papillary thyroid cancer (PTC) is associated with BRAF V600E mutation (40-50% of cases) and RET overexpression through juxtaposition to the PTC genes by chromosome fusion (5-40% of cases). Follicular thyroid carcinomas are specifically associated with PPARG-PAX8 gene fusions in 25-50% of cases. NRAS, HRAS and KRAS mutations are more commonly associated with follicular thyroid neoplasms than PTC.