Liquid Biopsy in Metastatic Prostate Cancer


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Jenny Antonello1,Jakub Chudziak1,Shambhavi Srivastava1,Adnan Syed1,Deborah Burt1,Mahmood Ayub1,Alan Redfern1,Bedirhan Kilerci1,Esther Baena1,Dominic Rothwell1,Noel Clarke2,Caroline Dive2,Ged Brady2
1CRUK,2cruk

Abstract

Background

Prostate cancer is the most common cancer in males in the UK, over  47,000 men are diagnosed with prostate cancer every year with more than 10,800 deaths. Prostate cancer is potentially curable but 20% of the patients develop metastatic disease. The initial treatment for metastatic disease is the androgen deprivation therapy (ADT). Nearly all men with metastatic disease develop resistance to ADT, stage called castration resistant prostate cancer developing eventually in mCRPC associate with poor prognosis and patients over treated. Tumour biopsies are the gold standard for CRPC tissue sampling but are generally invasive, difficult to collect longitudinally and can miss tumour heterogeneity. Circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA) measured in a patient’s peripheral blood sample allow the detection of tumour associated alterations such as copy number aberrations (CNA), single nucleotide variations and gene expression profiles. These liquid biopsies may be used to investigate tumour heterogeneity and to monitor clonal evolution during treatment

Method

Following plasma preparation and ctDNA isolation, next generation sequencing (NGS) libraries were prepared and whole genome sequencing carried out at a low depth (0.1−0.2X) using Illumina MiSeq platform to establish genome wide CNA from 22 mCRPC patients

Results

Blood samples from over 70 patients from Manchester Christie Hospital or Belfast Central Hospital were collected. CTC enumeration, enrichment and plasma isolation were performed and banked for all patients.  For 32 out of 77 patients, the CellSearch CTC number was more than 5 (indicated of poor prognosis).

Conclusion

ctDNA was extracted from 22 patients. Characteristic prostate associated CNA profiles were identified in the first 22 ctDNA patients analysed. On-going analysis on ctDNA and CTCs in matched samples for all banked patient samples are being assessed in a search for a liquid biopsy approach to personalised medicine in prostate cancer patients