Detection Rate of Actionable Mutations in Diverse Cancers Using a Biopsy-Free (Blood) Circulating Tumor Cell DNA Assay

Oncotarget. 2016 Mar 1;7(9):9707-17. doi: 10.18632/oncotarget.7110.

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.

Keywords: actionable alteration; cancer; ctDNA; liquid biopsy; personalized therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Biopsy
  • Class I Phosphatidylinositol 3-Kinases
  • DNA Copy Number Variations / genetics*
  • DNA, Neoplasm / genetics*
  • ErbB Receptors / genetics
  • Female
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Neoplasms / genetics*
  • Neoplastic Cells, Circulating / pathology*
  • Phosphatidylinositol 3-Kinases / genetics
  • Proto-Oncogene Proteins c-met / genetics
  • Receptor, Notch1 / genetics
  • Retrospective Studies
  • Tumor Suppressor Protein p53 / genetics
  • Young Adult

Substances

  • Biomarkers, Tumor
  • DNA, Neoplasm
  • NOTCH1 protein, human
  • Receptor, Notch1
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Phosphatidylinositol 3-Kinases
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • EGFR protein, human
  • ErbB Receptors
  • MET protein, human
  • Proto-Oncogene Proteins c-met