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Title: mRNA and microRNA expression profiles in circulating tumor cells and primary tumors of metastatic breast cancer patients
Authors: Sieuwerts, Anieta M.
Mostert, Bianca
Bolt-De Vries, Joan
Peeters, Dieter
De Jongh, Felix E.
Stouthard, Jacqueline M.L.
Dirix, Luc Y.
Van Dam, Peter A.
Van Galen, Anne
De Weerd, Vanja
Kraan, Jaco
Van Der Spoel, Petra
Ramírez-Moreno, Raquel 
Van Deurzen, Carolien H.M.
Smid, Marcel
Yu, Jack X.
Jiang, John
Wang, Yixin
Gratama, Jan W.
Sleijfer, Stefan
Foekens, John A.
Martens, John W.M.
Keywords: Gene-Expression
Molecular Markers
Prognosis, et al
Issue Date: 2011
Publisher: 1078-0432
Journal: Clinical Cancer Research 
Abstract: Purpose: Molecular characterization of circulating tumor cells (CTC) holds great promise. Unfortunately, routinely isolated CTC fractions currently still contain contaminating leukocytes, which makes CTC-specific molecular characterization extremely challenging. In this study, we determined mRNA and microRNA (miRNA) expression of potentially CTC-specific genes that are considered to be clinically relevant in breast cancer.Experimental Design: CTCs were isolated with the epithelial cell adhesion molecule-based CellSearch Profile Kit. Selected genes were measured by real-time reverse transcriptase PCR in CTCs of 50 metastatic breast cancer patients collected before starting first-line systemic therapy in blood from 53 healthy blood donors (HBD) and in primary tumors of 8 of the patients. The molecular profiles were associated with CTC counts and clinical parameters and compared with the profiles generated from the corresponding primary tumors.Results: We identified 55 mRNAs and 10 miRNAs more abundantly expressed in samples from 32 patients with at least 5 CTCs in 7.5 mL of blood compared with samples from 9 patients without detectable CTCs and HBDs. Clustering analysis resulted in 4 different patient clusters characterized by 5 distinct gene clusters. Twice the number of patients from cluster 2 to 4 had developed both visceral and nonvisceral metastases. Comparing transcript levels in CTCs with those measured in corresponding primary tumors showed clinically relevant discrepancies in estrogen receptor and HER2 levels.Conclusions: Our study shows that molecular profiling of low numbers of CTCs in a high background of leukocytes is feasible and shows promise for further studies on the clinical relevance of molecular characterization of CTCs. Clin Cancer Res; 17(11); 3600-18. (C)2011 AACR.
ISSN: 1078-0432
DOI: 10.1158/1078-0432.CCR-11-0255
Source: Clinical Cancer Research[ISSN 1078-0432],v. 17, p. 3600-3618
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