Plasma circulating tumor DNA as an alternative to metastatic biopsies for mutational analysis in breast cancer
- 1 October 2014
- journal article
- research article
- Published by Elsevier BV in Annals Of Oncology
- Vol. 25 (10), 1959-1965
- https://doi.org/10.1093/annonc/mdu288
Abstract
Molecular screening programs use next-generation sequencing (NGS) of cancer gene panels to analyze metastatic biopsies. We interrogated whether plasma could be used as an alternative to metastatic biopsies. The Ion AmpliSeq™ Cancer Hotspot Panel v2 (Ion Torrent), covering 2800 COSMIC mutations from 50 cancer genes was used to analyze 69 tumor (primary/metastases) and 31 plasma samples from 17 metastatic breast cancer patients. The targeted coverage for tumor DNA was ×1000 and for plasma cell-free DNA ×25 000. Whole blood normal DNA was used to exclude germline variants. The Illumina technology was used to confirm observed mutations. Evaluable NGS results were obtained for 60 tumor and 31 plasma samples from 17 patients. When tumor samples were analyzed, 12 of 17 (71%, 95% confidence interval (CI) 44% to 90%) patients had ≥1 mutation (median 1 mutation per patient, range 0-2 mutations) in either p53, PIK3CA, PTEN, AKT1 or IDH2 gene. When plasma samples were analyzed, 12 of 17 (71%, 95% CI: 44-90%) patients had ≥1 mutation (median 1 mutation per patient, range 0-2 mutations) in either p53, PIK3CA, PTEN, AKT1, IDH2 and SMAD4. All mutations were confirmed. When we focused on tumor and plasma samples collected at the same time-point, we observed that, in four patients, no mutation was identified in either tumor or plasma; in nine patients, the same mutations was identified in tumor and plasma; in two patients, a mutation was identified in tumor but not in plasma; in two patients, a mutation was identified in plasma but not in tumor. Thus, in 13 of 17 (76%, 95% CI 50% to 93%) patients, tumor and plasma provided concordant results whereas in 4 of 17 (24%, 95% CI 7% to 50%) patients, the results were discordant, providing complementary information. Plasma can be prospectively tested as an alternative to metastatic biopsies in molecular screening programs.Keywords
Funding Information
- Fonds de la Recherche Scientifique
- Breast Cancer Research Foundation
- MEDIC foundation
- OncoDNA
- Les amis de l'Institut Bordet
This publication has 19 references indexed in Scilit:
- Liquid Biopsies: Genotyping Circulating Tumor DNAJournal of Clinical Oncology, 2014
- Comparative genomic hybridisation array and DNA sequencing to direct treatment of metastatic breast cancer: a multicentre, prospective trial (SAFIR01/UNICANCER)The Lancet Oncology, 2014
- Luminal breast cancer: from biology to treatmentNature Reviews Clinical Oncology, 2013
- Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNANature, 2013
- Analysis of Circulating Tumor DNA to Monitor Metastatic Breast CancerNew England Journal of Medicine, 2013
- Cancer incidence and mortality patterns in Europe: Estimates for 40 countries in 2012European Journal Of Cancer, 2013
- Comprehensive molecular portraits of human breast tumoursNature, 2012
- The landscape of cancer genes and mutational processes in breast cancerNature, 2012
- Cell-free nucleic acids as biomarkers in cancer patientsNature Reviews Cancer, 2011
- Development of Personalized Tumor Biomarkers Using Massively Parallel SequencingScience Translational Medicine, 2010