The influence of the long life-history of prostate cancer on the temporal and spatial variability of the tumour genome is now being elucidated. Multiregion sequencing to identify spatio-genomic differences in prostate tumour mutation profiles combined with computational approaches can map the evolution and transit of tumour cells throughout an individual patient.
A series of recent studies have demonstrated that a prostate tumour is often composed of different subclones, with varying genetic similarity. As such, a single biopsy specimen may be insufficient to make accurate clinical predictions from molecular biomarkers, greatly complicating the application of biopsy-based tools for precision medicine. In addition, subclones that arise outside of the primary tumour can seed new metastases and circulate between sites within a patient.
The mutational complexity of multiple tumour clones within the same individual, which respond differently to specific treatments, suggests the need for multimodal interventions.
aDepartment of Medical Biophysics, University of Toronto
bInformatics and Biocomputing Program, Ontario Institute for Cancer Research
cDepartment of Pharmacology and Toxicology, University of Toronto
dPrincess Margaret Cancer Centre, University Health Network
eDepartment of Pathology, Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada
Correspondence to Robert G. Bristow, Department of Radiation Oncology, Princess Margaret Cancer Centre, 5th Floor, 610 University Avenue, Toronto, ON M5G 2M9, Canada. E-mail: Bristow@rmp.uhn.on.ca