Abstract PD04-10: Genome-Wide Copy Number Analysis of Circulating Tumor Cells (CTCs) from Metastatic Breast Cancer Patients

• Published in: Cancer research (Chicago, Ill.) Vol. 70; no. 24_Supplement; p. PD04-10
• Main Authors: Magbanua, MJM, Sosa, EV, Scott, JH, Pinkel, D, Rugo, HS, Park, JW
• Format: Journal Article
• Language: English
• Published: 15.12.2010
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.SABCS10-PD04-10

Abstract Background: Clinical studies have demonstrated the prognostic and predictive value of the number of CTCs in metastatic breast cancer. However, it is the molecular characterization of CTCs that offers insight into the biology of these tumor cells in the context of personalized treatment. Methods: Ten to twenty mLs of blood from 32 metastatic breast cancer patients with poor prognosis (≥5 CTCs in 7.5mLs blood) were subjected to immunomagnetic enrichment. Pools of ∼20 CTCs [EpCAM+, CD45-, nucleated] were isolated via fluorescence activated cell sorting, FACS. Genomic DNA was subjected to whole genome amplification followed by array comparative genomic hybridization (CGH) analysis. Serial genomic profiling was performed in three patients. Genomic profiles from archival primary tumor available from 4 patients were compared to matched CTCs. Copy number analysis was performed using the Nexus® Copy Number. Genomic alterations with p ≥0.05 were considered significant. Results: Genomic profiling of CTCs revealed significant recurrent (≥35%) genomic alterations including gains in 8q12.1, 8q24 and losses in 1p36, 4p16, 5q21, 10q22, 11q24-25, and 13q34. Good concordance of CGH profiles obtained from CTCs isolated from serial blood samples attested to the reproducibility of the assay. Furthermore, comparisons of CTCs with matched archival primary tumors confirmed shared lineage with some divergence. Conclusions: Copy number analysis revealed common genomic alterations in CTCs as well as shared aberrations with matched primary tumor. In addition, we demonstrated the feasibility of serial genomic profiling of CTCs. Future work will determine associations between genomic aberrations in CTCs and clinicopathological parameters. Uncovering genomic alterations in CTCs may lead to the discovery of therapeutic biomarkers to specifically target these cells in breast cancer patients who respond poorly to current aggressive therapies. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD04-10.