Genomic profiling of isolated circulating tumor cells from metastatic breast cancer patients
Menée à partir de cellules tumorales circulantes isolées dans le sang de 181 patientes atteintes d'un cancer métastatique du sein, cette étude évalue la faisabilité d'une nouvelle technologie permettant de procéder à une analyse des anomalies du nombre de copies de gènes dans le génome tumoral
Molecular characterization of circulating tumor cells (CTCs) from blood is technically challenging because cells are rare and difficult to isolate. We developed a novel approach to isolate CTCs from blood via immunomagnetic enrichment followed by fluorescence activated cell sorting (IE/FACS). Isolated CTCs were subjected to genome-wide copy number analysis via array comparative genomic hybridization (aCGH). In clinical studies, CTCs were isolated from 181 patients with metastatic breast cancer, 102 of which were successfully profiled, including matched archival primary tumor from five patients. CTCs revealed a wide range of copy number alterations including those previously reported in breast cancer. Comparison with two published aCGH datasets of primary breast tumors revealed similar frequencies of recurrent genomic copy number aberrations. In addition, serial testing of CTCs confirmed reproducibility and indicated genomic change over time. Comparison of CTCs with matched archival primary tumors confirmed shared lineage with notable divergence. We demonstrate that it is feasible to isolate CTCs away from hematopoietic cells with high purity via IE/FACS and profile them via aCGH analysis. Our approach may be utilized to explore genomic events involved in cancer progression and to monitor therapeutic efficacy of targeted therapies in clinical trials in a relatively non-invasive manner.
Cancer Research , résumé, 2012