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Cited by 533Prostate Cancer Treatment and ResearchCancer Genomics and DiagnosticsChromatin Remodeling and Cancer

Characterization of ERG , AR and PTEN Gene Status in Circulating Tumor Cells from Patients with Castration-Resistant Prostate Cancer

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Attard, Gerhardt, Swennenhuis, Joost F., Olmos, David, Reid, Alison H.M., Vickers, Elaine, A'Hern, Roger, Levink, Rianne, Coumans, Frank +16 more·2009·Cancer Research
DOI 10.1158/0008-5472.can-08-3667

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Abstract

Hormone-driven expression of the ERG oncogene after fusion with TMPRSS2 occurs in 30% to 70% of therapy-naive prostate cancers. Its relevance in castration-resistant prostate cancer (CRPC) remains controversial as ERG is not expressed in some TMPRSS2-ERG androgen-independent xenograft models. However, unlike these models, CRPC patients have an increasing prostate-specific antigen, indicating active androgen receptor signaling. Here, we collected blood every month from 89 patients (54 chemotherapy-naive patients and 35 docetaxel-treated patients) treated in phase I/phase II clinical trials of an orally available, highly specific CYP17 inhibitor, abiraterone acetate, that ablates the synthesis of androgens and estrogens that drive TMPRSS2-ERG fusions. We isolated circulating tumor cells (CTC) by anti–epithelial cell adhesion molecule immunomagnetic selection followed by cytokeratin and CD45 immunofluorescence and 4′,6-diamidino-2-phenylindole staining. We used multicolor fluorescence in situ hybridization to show that CRPC CTCs, metastases, and prostate tissue invariably had the same ERG gene status as therapy-naive tumors (n = 31). We then used quantitative reverse transcription–PCR to show that ERG expression was maintained in CRPC. We also observed homogeneity in ERG gene rearrangement status in CTCs (n = 48) in contrast to significant heterogeneity of AR copy number gain and PTEN loss, suggesting that rearrangement of ERG may be an earlier event in prostate carcinogenesis. We finally report a significant association between ERG rearrangements in therapy-naive tumors, CRPCs, and CTCs and magnitude of prostate-specific antigen decline (P = 0.007) in CRPC patients treated with abiraterone acetate. These data confirm that CTCs are malignant in origin and indicate that hormone-regulated expression of ERG persists in CRPC. [Cancer Res 2009;69(7):2912–8]

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  • Most prostate cancers express AR throughout the course of the disease.

    “Most PCas express AR throughout the course of the disease2–5”

    From Genome-scale CRISPR screens identify PTGES3 as a direct modulator of androgen receptor function in advanced prostate cancer (2025) · cites this paper as [3]

    The Introduction says that rising PSA in castration-resistant prostate cancer indicates active androgen receptor (AR) signaling. That supports AR activity in advanced disease, but the paper does not establish that most prostate cancers express AR throughout the course of disease; its longitudinal findings concern ERG, not AR. Page numbers are unavailable in our copy. (LLM, conf=0.82)

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  1. Olmos D, Arkenau HT, Ang JE, et al. Circulating tumor cell as intermediate end points in castration- resistant prostate cancer. Ann Oncol 2008;20:27-33.

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Authors
Attard, G., Swennenhuis, J. F., Olmos, D., Reid, A. H. M., Vickers, E., A'Hern, R., Levink, R., Coumans, F., Moreira, J., Riisnaes, R., Oommen, N. B., Hawche, G., Jameson, C., Thompson, E., Sipkema, R., Carden, C. P., Parker, C., Dearnaley, D., Kaye, S. B., Cooper, C. S., Molina, A., Cox, M. E., Terstappen, L. W. M. M., & de Bono, J. S.
Affiliations
  • Royal Marsden NHS Foundation Trust (GB)
  • University of Twente (NL)
  • 5Prostate Cancer Center, Vancouver, British Columbia, Canada; and
  • 1The Institute of Cancer Research, Sutton, Surrey, United Kingdom;
  • 4Immunicon/Veridex, Enschede, the Netherlands;
  • Institute of Cancer Research (GB)
  • Los Angeles Police Department (US)
ORCID
Venue
Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2009-04-01
Volume
69
Issue
7
Pages
2912-2918
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
DOI
10.1158/0008-5472.can-08-3667
OpenAlex
W2131456094
Cited by
533
References
23
Citations by year
2026: 4 · 2025: 6 · 2024: 6 · 2023: 6 · 2022: 15 · 2021: 11 · 2020: 17 · 2019: 23 · 2018: 23 · 2017: 42 · 2016: 53 · 2015: 38 · 2014: 63 · 2013: 52 · 2012: 57
FWCI
48.06
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
  • University of Twente Research Information (submittedVersion, other-oa)
  • UEA Digital Repository (University of East Anglia) (submittedVersion)
Funders
  • Cancer Research UK
  • National Institute for Health and Care Research (CL-2008-22-001, C51/A7401)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords
castration-resistant prostate cancer, circulating tumor cells, TMPRSS2-ERG fusion, PTEN loss, abiraterone, CYP17 inhibitors, tumor heterogeneity, prostate carcinogenesis, hormone-regulated gene expression
MeSH terms
Transcriptional Regulator ERG, Epithelial Cell Adhesion Molecule, Androstenes, Androstenols, Antigens, Neoplasm, Humans, Keratins, Male, Neoplastic Cells, Circulating, Neoplasms, Hormone-Dependent, Prostatic Neoplasms, Receptors, Androgen, Oncogene Proteins, Fusion, Trans-Activators, Cell Adhesion Molecules, In Situ Hybridization, Fluorescence, Immunomagnetic Separation, Gene Order, PTEN Phosphohydrolase

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