Punctuated evolution of prostate cancer genomes. Academic Article uri icon

Overview

abstract

  • The analysis of exonic DNA from prostate cancers has identified recurrently mutated genes, but the spectrum of genome-wide alterations has not been profiled extensively in this disease. We sequenced the genomes of 57 prostate tumors and matched normal tissues to characterize somatic alterations and to study how they accumulate during oncogenesis and progression. By modeling the genesis of genomic rearrangements, we identified abundant DNA translocations and deletions that arise in a highly interdependent manner. This phenomenon, which we term "chromoplexy," frequently accounts for the dysregulation of prostate cancer genes and appears to disrupt multiple cancer genes coordinately. Our modeling suggests that chromoplexy may induce considerable genomic derangement over relatively few events in prostate cancer and other neoplasms, supporting a model of punctuated cancer evolution. By characterizing the clonal hierarchy of genomic lesions in prostate tumors, we charted a path of oncogenic events along which chromoplexy may drive prostate carcinogenesis.

authors

publication date

  • April 25, 2013

Research

keywords

  • Chromosome Aberrations
  • Gene Expression Regulation, Neoplastic
  • Genome, Human
  • Prostatic Neoplasms

Identity

PubMed Central ID

  • PMC3690918

Scopus Document Identifier

  • 84875757638

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2013.03.021

PubMed ID

  • 23622249

Additional Document Info

volume

  • 153

issue

  • 3