Clonality of localized and metastatic prostate cancer

Curr Opin Urol. 2016 May;26(3):219-24. doi: 10.1097/MOU.0000000000000279.

Abstract

Purpose of review: 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.

Recent findings: 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.

Summary: The mutational complexity of multiple tumour clones within the same individual, which respond differently to specific treatments, suggests the need for multimodal interventions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Ataxia Telangiectasia Mutated Proteins / genetics*
  • Biopsy / methods
  • Class I Phosphatidylinositol 3-Kinases
  • Combined Modality Therapy
  • DNA Mutational Analysis
  • Genomics
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Mutation*
  • Oncogene Proteins, Fusion / genetics*
  • Phosphatidylinositol 3-Kinases / genetics*
  • Polymorphism, Single Nucleotide
  • Precision Medicine
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / therapy
  • Receptors, Androgen / genetics*
  • Sequence Analysis, DNA

Substances

  • AR protein, human
  • Oncogene Proteins, Fusion
  • Receptors, Androgen
  • TMPRSS2-ERG fusion protein, human
  • Phosphatidylinositol 3-Kinases
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins