Faculty Collaboration Database

BRAF Mutation Testing in Cell-Free DNA from the Plasma of Patients with Advanced Cancers Using a Rapid, Automated Molecular Diagnostics System. Mol Cancer Ther 2016 Jun;15(6):1397-404

Date

05/22/2016

Pubmed ID

27207774

DOI

10.1158/1535-7163.MCT-15-0712

Scopus ID

2-s2.0-84971516426 (requires institutional sign-in at Scopus site)   70 Citations

Abstract

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 BRAF(V600) status from formalin-fixed paraffin-embedded (FFPE) tumors were tested using a prototype version of the Idylla BRAF Mutation Test, a fully integrated real-time PCR-based test with turnaround time about 90 minutes. Of 160 patients, BRAF(V600) 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%; κ, 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 BRAF(V600) 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 BRAF(V600) cfDNA were associated with longer TTF (P = 0.045). In conclusion, testing for BRAF(V600) mutations in plasma cfDNA using the Idylla BRAF Mutation Test has acceptable concordance with standard testing of tumor tissue. A higher percentage of mutant BRAF(V600) in cfDNA corresponded with shorter OS and in patients receiving BRAF/MEK inhibitors also with shorter TTF. Mol Cancer Ther; 15(6); 1397-404. ©2016 AACR.

Author List

Janku F, Huang HJ, Claes B, Falchook GS, Fu S, Hong D, Ramzanali NM, Nitti G, Cabrilo G, Tsimberidou AM, Naing A, Piha-Paul SA, Wheler JJ, Karp DD, Holley VR, Zinner RG, Subbiah V, Luthra R, Kopetz S, Overman MJ, Kee BK, Patel S, Devogelaere B, Sablon E, Maertens G, Mills GB, Kurzrock R, Meric-Bernstam F

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aged, 80 and over
Cell Line, Tumor
Cell-Free System
DNA Mutational Analysis
Early Detection of Cancer
Female
Humans
Male
Melanoma
Middle Aged
Prognosis
Proto-Oncogene Proteins B-raf
Sensitivity and Specificity
Skin Neoplasms
Survival Analysis
Young Adult