Abstract 3094
Background
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.
Methods
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.
Results
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.
Conclusions
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.
Funding
Prostate Cancer Foundation, National Cancer Institute SPORE P50-CA211024, and Epic Sciences.
Disclosure
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.
Resources from the same session
3073 - 1 patient 3 different advance Ca nurse’s roles: symptom management&continuum care through a joint approach in a clinical case
Presenter: Catarina Almeida
Session: Poster Display session 3
Resources:
Abstract
4527 - Identification of malnutrition risk factors in patients with cancer in the first nursing visit
Presenter: Amaia Valverde
Session: Poster Display session 3
Resources:
Abstract
2904 - Engaging Cancer Survivors, Healthcare Providers and Advocates in The Development of a Colorectal Cancer Survivorship Information Resource: A Participatory Action Research Study
Presenter: Amanda Drury
Session: Poster Display session 3
Resources:
Abstract
3435 - Medical nurses’ experiences of the care-needs of adult patients with a primary brain tumour
Presenter: Jamila Mohammed
Session: Poster Display session 3
Resources:
Abstract
857 - Feasibility and acceptability of a mHealth intervention to increase colonoscopy uptake among Chinese first-degree relatives: a pilot cluster randomized controlled trial
Presenter: Yang Bai
Session: Poster Display session 3
Resources:
Abstract
1087 - Cancer patient participation and compliance in microbiome sample collection: an oncology research nurse’s experience
Presenter: Julie Malo
Session: Poster Display session 3
Resources:
Abstract
2783 - Implementing Digital Individual Care plans for Patients with Head and Neck cancer- Challenges and opportunities
Presenter: Helena Ullgren
Session: Poster Display session 3
Resources:
Abstract
1152 - The Effect of the Short-term and Long-term Compassion Fatigue Resiliency Program on the Quality of Life, Perceived Stress and Psychological Resilience of Oncology-Hematology Nurses
Presenter: Tugba Pehlivan
Session: Poster Display session 3
Resources:
Abstract
1172 - Competing risk analyses of overall survival and cancer-specific survival in patients with orbital rhabdomyosarcoma after surgery: a large cohort study
Presenter: Yu Zhang
Session: Poster Display session 3
Resources:
Abstract
5949 - Communication of genetic information to family members in hereditary cancers and healthcare providers’ role
Presenter: Carla Pedrazzani
Session: Poster Display session 3
Resources:
Abstract