Faculty Collaboration Database

Detection rate of actionable mutations in diverse cancers using a biopsy-free (blood) circulating tumor cell DNA assay. Oncotarget 2016 Mar 01;7(9):9707-17

Date

02/06/2016

Pubmed ID

26848768

Pubmed Central ID

PMC4891078

DOI

10.18632/oncotarget.7110

Scopus ID

2-s2.0-84961636991 (requires institutional sign-in at Scopus site)   119 Citations

Abstract

Analysis of cell-free DNA using next-generation sequencing (NGS) is a powerful tool for the detection/monitoring of alterations present in circulating tumor DNA (ctDNA). Plasma extracted from 171 patients with a variety of cancers was analyzed for ctDNA (54 genes and copy number variants (CNVs) in three genes (EGFR, ERBB2 and MET)). The most represented cancers were lung (23%), breast (23%), and glioblastoma (19%). Ninety-nine patients (58%) had at least one detectable alteration. The most frequent alterations were TP53 (29.8%), followed by EGFR (17.5%), MET (10.5%), PIK3CA (7%), and NOTCH1 (5.8%). In contrast, of 222 healthy volunteers, only one had an aberration (TP53). Ninety patients with non-brain tumors had a discernible aberration (65% of 138 patients; in 70% of non-brain tumor patients with an alteration, the anomaly was potentially actionable). Interestingly, nine of 33 patients (27%) with glioblastoma had an alteration (6/33 (18%) potentially actionable). Overall, sixty-nine patients had potentially actionable alterations (40% of total; 69.7% of patients (69/99) with alterations); 68 patients (40% of total; 69% of patients with alterations), by a Food and Drug Administration (FDA) approved drug. In summary, 65% of diverse cancers (as well as 27% of glioblastomas) had detectable ctDNA aberration(s), with the majority theoretically actionable by an approved agent.

Author List

Schwaederle M, Husain H, Fanta PT, Piccioni DE, Kesari S, Schwab RB, Banks KC, Lanman RB, Talasaz A, Parker BA, 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
Biopsy
Class I Phosphatidylinositol 3-Kinases
DNA Copy Number Variations
DNA, Neoplasm
ErbB Receptors
Female
High-Throughput Nucleotide Sequencing
Humans
Male
Middle Aged
Mutation
Neoplasms
Neoplastic Cells, Circulating
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-met
Receptor, Notch1
Retrospective Studies
Tumor Suppressor Protein p53
Young Adult