Clinical utility of a blood-based BRAF(V600E) mutation assay in melanoma

Mol Cancer Ther. 2014 Dec;13(12):3210-8. doi: 10.1158/1535-7163.MCT-14-0349. Epub 2014 Oct 15.


BRAF inhibitors (BRAFi) have led to clinical benefit in patients with melanoma. The development of a blood-based assay to detect and quantify BRAF levels in these patients has diagnostic, prognostic, and predictive capabilities that could guide treatment decisions. Blood BRAF(V600E) detection and quantification were performed on samples from 128 patients with stage II (19), III (67), and IV (42) melanoma. Tissue BRAF analysis was performed in all patients with stage IV disease and in selected patients with stage II and III disease. Clinical outcomes were correlated to initial BRAF levels as well as BRAF level dynamics. Serial analysis was performed on 17 stage IV melanoma patients treated with BRAFi and compared with tumor measurements by RECIST. The assay was highly sensitive (96%) and specific (95%) in the stage IV setting, using a blood level of 4.8 pg as "positive." BRAF levels typically decreased following BRAFi. A subset of these patients (5) had an increase in BRAF(V600E) values 42 to 112 days before clinical or radiographic disease progression (PD). From 86 patients with resected, stage II or III melanoma, 39 had evidence of disease relapse (45.3%). Furthermore, BRAF mutation in the blood after surgical resection in these patients was not associated with a difference in relapse risk, although tissue BRAF status was only available for a subset of patients. In summary, we have developed a highly sensitive and specific, blood-based assay to detect BRAF(V600) mutation in patients with melanoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Cell Line, Tumor
  • Codon
  • DNA Mutational Analysis / methods*
  • DNA Mutational Analysis / standards
  • Genotype
  • Humans
  • Leukocytes, Mononuclear
  • Melanoma / diagnosis*
  • Melanoma / drug therapy
  • Melanoma / genetics*
  • Molecular Targeted Therapy
  • Mutation*
  • Neoplasm Staging
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors
  • Proto-Oncogene Proteins B-raf / genetics*
  • Reproducibility of Results
  • Sensitivity and Specificity


  • Codon
  • Proto-Oncogene Proteins B-raf