Faculty Collaboration Database

Actionable mutations in plasma cell-free DNA in patients with advanced cancers referred for experimental targeted therapies. Oncotarget 2015 May 20;6(14):12809-21

Date

05/20/2015

Pubmed ID

25980577

Pubmed Central ID

PMC4494976

DOI

10.18632/oncotarget.3373

Scopus ID

2-s2.0-84930025659 (requires institutional sign-in at Scopus site)   80 Citations

Abstract

Cell-free (cf) DNA in the plasma of cancer patients offers an easily obtainable source of biologic material for mutation analysis. Plasma samples from 157 patients with advanced cancers who progressed on systemic therapy were tested for 21 mutations in BRAF, EGFR, KRAS, and PIK3CA using the BEAMing method and results were compared to mutation analysis of archival tumor tissue from a CLIA-certified laboratory obtained as standard of care from diagnostic or therapeutic procedures. Results were concordant for archival tissue and plasma cfDNA in 91% cases for BRAF mutations (kappa = 0.75, 95% confidence interval [CI] 0.63 - 0.88), in 99% cases for EGFR mutations (kappa = 0.90, 95% CI 0.71- 1.00), in 83% cases for KRAS mutations (kappa = 0.67, 95% CI 0.54 - 0.80) and in 91% cases for PIK3CA mutations (kappa = 0.65, 95% CI 0.46 - 0.85). Patients (n = 41) with > 1% of KRAS mutant cfDNA had a shorter median survival compared to 20 patients with </= 1% of KRAS mutant DNA (4.8 vs. 7.3 months, p=0.008). Similarly, 67 patients with >1% of mutant cfDNA (BRAF, EGFR, KRAS, or PIK3CA) had a shorter median survival compared to 33 patients with </= 1% of mutant cfDNA (5.5 vs. 9.8 months, p = 0.001), which was confirmed in multivariable analysis. [Corrected]

Author List

Janku F, Angenendt P, Tsimberidou AM, Fu S, Naing A, Falchook GS, Hong DS, Holley VR, Cabrilo G, Wheler JJ, Piha-Paul SA, Zinner RG, Bedikian AY, Overman MJ, Kee BK, Kim KB, Kopetz ES, Luthra R, Diehl F, Meric-Bernstam F, Kurzrock R

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
Biomarkers, Tumor
Class I Phosphatidylinositol 3-Kinases
DNA Mutational Analysis
DNA, Neoplasm
Female
Genes, erbB-1
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Neoplasms
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins B-raf
Proto-Oncogene Proteins p21(ras)
Young Adult