We have performed deep genomic analysis of matching primary and metastatic prostate tumours from a unique cohort of patients, revealing for the first time, the precise patterns and direction of lethal metastatic spread as well as determined the tumor subclonal complexity at primary and metastatic sties. Analysis of mutations associated with metastasis has revealed an enrichment of particular mutations linked with expansion of subclones with metastatic potential which can be detected in the blood. We now aim to comprehensively annotate the subclonal complexity of primary prostate tumors then track the subclones that go on to metastasize at distant sites and precisely monitor the blood, the dynamics of tumor subclonal complexity during the disease course.This project will permit us to derive for the first time robust signatures and candidate drivers of tumour subclonal expansion and metastasis that could aid with lethal risk prostate cancer stratification.
The study of tumour evolution and dynamics, particularly in prostate cancer, has largely been hamstrung due to lack of multiple, quality high-depth whole-genome sequencing samples from the same patient. Our most recent project has generated multiple whole-genome libraries of around two dozen patients with metastatic advanced prostate cancer, as well as biopsies before and after hormone therapy. knowledge of prostate cancer metastasis, and tumour resistance mechanisms in response to hormonal therapy, are largely incomplete. Hence, comprehensive genetic and transcriptomic analyses of our samples, holds great potential to uncover pertinent mechanisms with clinical applications. We aim to utilise bioinformatics techniques to uncover clinically relevant variants, biomarkers and/or patterns, to improve understanding of prostate cancer metastasises, and response to hormonal treatment.