Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster Display session 3

3094 - Circulating tumor cell (CTC) genomic landscape in neuroendocrine prostate cancer (NEPC) by single cell copy number analysis


30 Sep 2019


Poster Display session 3


Tumour Site

Prostate Cancer


Vincenza Conteduca


Annals of Oncology (2019) 30 (suppl_5): v325-v355. 10.1093/annonc/mdz248


V. Conteduca1, S. Ku1, Y. Wang2, L. Fernandez2, M. Kearney2, J. Lee2, R. Jiles2, A. rodriguez2, D.M. Nanus3, S.T. Tagawa3, R. Dittamore4, H. Beltran1

Author affiliations

  • 1 Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, 02115 - Boston/US
  • 2 Translational Research, Epic Sciences, 92121 - San Diego/US
  • 3 Oncology, Weill Cornell Medicine, 10065 - New York/US
  • 4 Translational Research, Epic Sciences Inc., 92121 - San Diego/US


Login to access the resources on OncologyPRO.

If you do not have an ESMO account, please create one for free.

Abstract 3094


Cell-to-cell heterogeneity is a major driver of cancer evolution, progression, and drug resistance. NEPC is an aggressive variant of prostate cancer that may develop from pre-existing prostate adenocarcinoma as a mechanism of treatment resistance. Loss of tumour suppressors RB1, TP53, PTEN are frequent in NEPC but also present in a subset of prostate adenocarcinoma. Through single-cell CTC genomics of men with castration resistant adenocarcinoma (CRPC-Adeno) and NEPC, we aimed to characterize the clonal heterogeneity that underlies these resistance scenarios.


CTCs were assessed using Epic Sciences platform for morphology and expression of adenocarcinoma (AR) and NEPC (DLL3) markers. Low pass whole genome sequencing was performed on individual cells/clusters. CTC copy number alterations (CNAs) were compared with whole exome sequencing data of patient-matched tumor biopsies.


A total of 182 CTCs from 13 pts (5 CRPC, 8 NEPC) with matched biopsies were analyzed for 87 commonly altered prostate cancer genes. 11 pts (7 NEPC and 4 CRPC-Adeno, 177 CTCs) had at least 3 CTCs with one or more gene CNA. Concordance of these alterations with matched biopsy was 90.9%. All 7 NEPC pts had at least one tumor RB1,TP53, or PTEN loss; 71.4% (5/7) pts had loss of > two tumor suppressors, of which 40.6% (43/106) of CTCs harbored alterations in the same cell (vs. different cells). In contrast, only 2/4 CRPC-Adeno pts had one RB1/TP53/PTEN loss and loss of > 2 occurred in none. Combined loss of RB1, TP53 and/or PTEN in CTCs was associated with lower AR expression and higher DLL3 expression in CTCs. Other CNAs showed similar trends, with higher concordance of alterations across CTCs in individuals with NEPC.


Prostate cancer associated CNA profiles of single cell CTCs was consistent with matched metastatic tumor biopsies in our cohort. Combined loss of tumour suppressor genes is more frequent in NEPC than in CRPC-Adeno and more often co-occurs in individual cells. Overall there is higher concordance, or less diversity (heterogeneity), across CTCs in NEPC. Analysis of additional patients including serial CTC assessment is ongoing.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.


Prostate Cancer Foundation, National Cancer Institute SPORE P50-CA211024, and Epic Sciences.


V. Conteduca: Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Travel / Accommodation / Expenses: Janssen; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Astellas; Travel / Accommodation / Expenses: Sanofi. Y. Wang: Full / Part-time employment: Epic Sciences. L. Fernandez: Full / Part-time employment: Epic Sciences. M. Kearney: Full / Part-time employment: Epic Sciences. J. Lee: Full / Part-time employment: Epic Sciences. R. Jiles: Full / Part-time employment: Epic Sciences. A. Rodriguez: Full / Part-time employment: Epic Sciences. R. Dittamore: Full / Part-time employment, Officer / Board of Directors: Epic Sciences. H. Beltran: Advisory / Consultancy: Janssen; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Astellas. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.