The Case for Laboratory Developed Procedures: Quality and Positive Impact on Patient Care

Kaul, Karen L.; Sabatini, Linda M.; Tsongalis, Gregory J.; Caliendo, Angela M.; Olsen, Randall J.; Ashwood, Edward R.; Bale, Sherri; Benirschke, Robert; Carlow, Dean; Funke, Birgit H.; Grody, Wayne W.; Hayden, Randall T.; Hegde, Madhuri; Lyon, Elaine; Murata, Kazunori; Pessin, Melissa; Press, Richard D.; Thomson, Richard B.

The Cobas 4800 BRAF V600 Mutation Test (Roche Molecular Systems, Pleasanton, CA, USA) sporadically cross reacts with BRAF V600K and BRAF V600D mutations 61,62 and thus is neither sensitive for BRAF V600 mutations nor specific for BRAF V600E mutations, confounding accurate outcome evaluations and preventing its usefulness in selecting patient for Tafinlar therapy. The THxID BRAF kit (bioMerieux, Boston, MA, USA) does detect both BRAF V600E and BRAF V600K mutations (but not other BRAF V600 mutations) and is necessary to distinguish between alternate therapeutic options (single agent vs combination therapy). It is important to note that increased cell proliferation has been seen in tumors treated with BRAF inhibitors with normal BRAF. 61 It is therefore important to identify all BRAF activating mutations to assist in the selection of appropriate therapy. The FDA-approved assays are therefore not adequate for current clinical needs.