BRAF Mutation testing in cell-free DNA from the plasma of patients with advanced cancers using a rapid, automated molecular diagnostics system

Filip Janku, Helen J. Huang, Bart Claes, Gerald S. Falchook, Siqing Fu, David Hong, Nishma M. Ramzanali, Giovanni Nitti, Goran Cabrilo, Apostolia M. Tsimberidou, Aung Naing, Sarina A. Piha-Paul, Jennifer J. Wheler, Daniel D. Karp, Veronica R. Holley, Ralph G. Zinner, Vivek Subbiah, Rajyalakshmi Luthra, Scott Kopetz, Michael J. OvermanBryan K. Kee, Sapna Patel, Benoit Devogelaere, Erwin Sablon, Geert Maertens, Gordon B. Mills, Razelle Kurzrock, Funda Meric-Bernstam

Research output: Contribution to journalArticlepeer-review

63 Scopus citations


Cell-free (cf) DNA from plasma offers an easily obtainable material for BRAF mutation analysis for diagnostics and response monitoring. In this study, plasma-derived cfDNA samples from patients with progressing advanced cancers or malignant histiocytosis with known BRAFV600 status from formalin-fixed paraffinembedded (FFPE) tumors were tested using a prototype version of the Idylla BRAF Mutation Test, a fully integrated real-time PCRbased test with turnaround time about 90 minutes. Of 160 patients, BRAFV600 mutations were detected in 62 (39%) archival FFPE tumor samples and 47 (29%) plasma cfDNA samples. The two methods had overall agreement in 141 patients [88%; k, 0.74; SE, 0.06; 95% confidence interval (CI), 0.63-0.85]. Idylla had a sensitivity of 73% (95% CI, 0.60-0.83) and specificity of 98% (95% CI, 0.93-1.00). A higher percentage, but not concentration, of BRAFV600 cfDNA in the wild-type background (>2% vs. ≤ 2%) was associated with shorter overall survival (OS; P= 0.005) and in patients with BRAF mutations in the tissue, who were receiving BRAF/MEK inhibitors, shorter time to treatment failure (TTF; P = 0.001). Longitudinal monitoring demonstrated that decreasing levels of BRAFV600 cfDNA were associated with longer TTF (P= 0.045). In conclusion, testing for BRAFV600 mutations in plasma cfDNA using the Idylla BRAF Mutation Test has acceptable concordance with standard testing of tumor tissue. A higher percentage of mutant BRAFV600 in cfDNA corresponded with shorter OS and in patients receiving BRAF/MEK inhibitors also with shorter TTF.

Original languageEnglish (US)
Pages (from-to)1397-1404
Number of pages8
JournalMolecular cancer therapeutics
Issue number6
StatePublished - Jun 2016
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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