BRAF V600E Mutation Testing

BRAF is a member of RAF family of serine/threonine kinases and mediates cellular responses to growth signals through the RAS-RAF-MAP kinase pathway.

BRAF mutations are found in approximately 15% of colorectal cancers (CRC), 60-70% of melanomas and approximately 45% of papillary thyroid carcinomas.

The most common mutation of the BRAF gene is a thymidine to adenine change at nucleotide 1799, resulting in an amino acid change from valine to glutamic acid at codon 600 (V600E). This alteration has been shown to activate the kinase activity of the BRAF.

The V600E BRAF mutation has been associated with resistance to the tyrosine kinase inhibitors, Panitumumab (Vectibix) and Cetuximab (Erbitux) in metastatic colorectal cancer.

There are currently early phase compounds being trialled that specifically inhibit BRAF at the V600E site in the hope of treating cancers such as melanoma or CRC. Early results have demonstrated a high degree of specificity with the drug targeting only the tumour cells containing the BRAF V600E mutation.

Specimen Required:

Formalin-fixed paraffin embedded tissue containing at least 20% tumour is required. Either of the following is acceptable.

    1 The entire tissue block can be sent which will be sectioned, macro-dissected and processed, then returned following analysis.

    2 Eight, seven micron unstained sections on labelled glass slides, together with one H&E stained section.

Assay Performed: Twice per week
Medicare Rebate: No

References:

Di Nicolantonio et al. Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol 2008; 26:5705-12.
Zhang et al. Novel approaches to treatment of advanced colorectal cancer with anti-EGFR monoclonal antibodies. Ann Med 2006 ;38:545-551.
Wong and Cunningham. Using predictive biomarkers to select patients with advanced colorectal cancer for treatment with epidermal growth factor receptor antibodies. J Clin Oncol 2008 ;26:35: 5668-5670.
Benvenuti et al. Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapy. Cancer Res 2007 ; 67:2643-2648.

Collection Centre Search