title: Clonality of localized and metastatic prostate cancer.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  The mutational complexity of multiple tumour clones within the same individual, which respond differently to specific treatments, suggests the need for multimodal interventions.
authors.affiliation: 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.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Boutros
authors.forename: Michael
authors.initials: M
authors.lastname: Fraser
authors.forename: Theodorus
authors.initials: T
authors.lastname: van der Kwast
authors.forename: Robert G
authors.initials: RG
authors.lastname: Bristow
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics*; D001706:Biopsy / Q000379:methods; D058534:Class I Phosphatidylinositol 3-Kinases; D003131:Combined Modality Therapy; D004252:DNA Mutational Analysis; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D009154:Mutation; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D011944:Receptors, Androgen / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: C410798:AR protein, human; D015514:Oncogene Proteins, Fusion; D011944:Receptors, Androgen; C515553:TMPRSS2-ERG fusion protein, human; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins