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PURPOSE: To assess the feasibility of characterizing gene copy number alteration by fluorescence in situ hybridization (FISH) of circulating tumor cells (CTC) isolated using the CellSearch system in patients with progressive castration-resistant metastatic prostate cancer. EXPERIMENTAL DESIGN: We used probe combinations that included the androgen receptor (AR) and MYC genes for FISH analysis of CTC samples collected from 77 men with castration-resistant metastatic prostate cancer. RESULTS: High-level chromosomal amplification of AR was detected in 38% and relative gain of MYC in 56% of samples analyzed. No such abnormalities were detected in samples with CTC counts of <10, reflecting ascertainment difficulty in these lower count samples. CONCLUSION: The CTC isolated from our patient cohort present a very similar molecular cytogenetic profile to that reported for late-stage tumors and show that FISH analysis of CTC can be a valuable, noninvasive surrogate for routine tumor profiling. That as many as 50% of these patients have substantial amplification of the AR locus indicates that androgen signaling continues to play an important role in late-stage prostate cancer.

Original publication

DOI

10.1158/1078-0432.CCR-08-2036

Type

Journal article

Journal

Clin Cancer Res

Publication Date

15/03/2009

Volume

15

Pages

2091 - 2097

Keywords

Gene Dosage, Genes, myc, Humans, In Situ Hybridization, Fluorescence, Male, Neoplastic Cells, Circulating, Prostatic Neoplasms, Receptors, Androgen