Plasma circulating tumor DNA as an alternative to metastatic biopsies for mutational analysis in breast cancer
Menée sur 17 patientes atteintes d'un cancer métastatique du sein, cette étude évalue la faisabilité d'une analyse de l'ADN circulant librement dans le plasma, à l'aide d'une technique de séquençage à haut débit, pour remplacer une biopsie des métastases
Background : 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.
Patients and methods : The Ion AmpliSeqTM Cancer Hotspot Panel v2 (Ion Torrent), covering 2,800 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 1000x and for plasma cell-free DNA 25000x. Whole blood normal DNA was used to exclude germline variants. The Illumina technology was used to confirm observed mutations.
Results : 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: 44-90%) 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 4 patients, no mutation was identified in either tumor or plasma, in 9 patients the same mutations was identified in tumor and plasma, in 2 patients a mutation was identified in tumor but not in plasma and in 2 patients a mutation was identified in plasma but not in tumor. Thus, in 13 of 17 (76%, 95%CI: 50-93%) patients, tumor and plasma provided concordant results whereas in 4 of 17 (24%, 95%CI:7-50%) patients, the results were discordant, providing complementary information.
Conclusion : Plasma can be prospectively tested as an alternative to metastatic biopsies in molecular screening programs.
Annals of Oncology , résumé, 2014