Pd56-05 a Germ-line Genetic Test for Prostate Cancer Risk (pgs-33) Together With a Family History Are Associated With Lethal Prostate Cancer
Year: 2018
Type: article
Abstract: between indolent and aggressive PCa can be inaccurate due to PCa heterogeneity and multi-focality.To compensate, many centres now take upwards of 20 biopsies of the prostate in one sitting, and monitor men with further biopsies to ensure that the disease is not progressing.There is therefore a need for a non-invasive biomarker than can monitor tumour heterogeneity and aggression.Circulating-tumour DNA (ctDNA) represents an exciting opportunity to monitor cancer status non-invasively.We developed a method for analysis of multiple genomic regions whilst retaining sensitivity for detection of individual mutant molecules, using multiplex replicate dilution sequencing, or MRD-Seq.METHODS: MRD-Seq distributes a DNA sample into multiple replicate PCR reactions, where each reaction contains a small number of initial template molecules.As a result, the detection of a single mutant molecule generates a signal that is clearly discernible above the background noise.Dilutions series determined the limit of detection (0.09% AF) and background noise (0.02%AF).To assess ctDNA detection in the context of intra-tumoural heterogeneity, prostatectomy specimens and pre-operative plasma was obtained from 2 men with localised but multifocal PCa, with appropriate ethical approval (MREC:01/4/061).Whole genome sequencing of spatially 5-7 distinct regions of prostate cancer for each man was used to design probes to interrogate private mutations.RESULTS: Plasma MRD-Seq demonstrated a mutant AF of 0.9% and 0.4% in the 2 men from ~1,000 genomic equivalent copies input.MRD-Seq detected the presence of private mutations from multiple private clones in the plasma, with evidence that more aggressive tumour regions (according to Gleason Grade) were over-represented in the plasma.CONCLUSIONS: This proof of principle study suggests that ctDNA is detectable in the plasma of localised PCa patients and could be used to monitor men on active surveillance and identify aggressive changes at an early stage.
Source: The Journal of Urology
Authors: Stephen Ryan, Michael Liss, Jae Choi, Fred Millard, Mike Randall, Sij Hemal, S. Lilly Zheng, Jianfeng Xu, Karim Kader
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2795411671