Integrated genome and transcriptome sequencing identifies a novel form of hybrid and aggressive prostate cancer. Academic Article uri icon

Overview

MeSH

  • Combined Modality Therapy
  • DNA, Neoplasm
  • Gene Amplification
  • Gene Dosage
  • Gene Expression Profiling
  • Gene Fusion
  • Humans
  • Male
  • Middle Aged
  • Neuroendocrine Cells
  • Prognosis
  • Prostatectomy
  • RNA-Binding Proteins
  • Sequence Analysis, DNA
  • Sequence Analysis, RNA

MeSH Major

  • Adenocarcinoma
  • Gene Expression Regulation, Neoplastic
  • Genomics
  • Prostatic Neoplasms

abstract

  • Next-generation sequencing is making sequence-based molecular pathology and personalized oncology viable. We selected an individual initially diagnosed with conventional but aggressive prostate adenocarcinoma and sequenced the genome and transcriptome from primary and metastatic tissues collected prior to hormone therapy. The histology-pathology and copy number profiles were remarkably homogeneous, yet it was possible to propose the quadrant of the prostate tumour that likely seeded the metastatic diaspora. Despite a homogeneous cell type, our transcriptome analysis revealed signatures of both luminal and neuroendocrine cell types. Remarkably, the repertoire of expressed but apparently private gene fusions, including C15orf21:MYC, recapitulated this biology. We hypothesize that the amplification and over-expression of the stem cell gene MSI2 may have contributed to the stable hybrid cellular identity. This hybrid luminal-neuroendocrine tumour appears to represent a novel and highly aggressive case of prostate cancer with unique biological features and, conceivably, a propensity for rapid progression to castrate-resistance. Overall, this work highlights the importance of integrated analyses of genome, exome and transcriptome sequences for basic tumour biology, sequence-based molecular pathology and personalized oncology. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

authors

publication date

  • May 2012

has subject area

  • Adenocarcinoma
  • Combined Modality Therapy
  • DNA, Neoplasm
  • Gene Amplification
  • Gene Dosage
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Fusion
  • Genomics
  • Humans
  • Male
  • Middle Aged
  • Neuroendocrine Cells
  • Prognosis
  • Prostatectomy
  • Prostatic Neoplasms
  • RNA-Binding Proteins
  • Sequence Analysis, DNA
  • Sequence Analysis, RNA

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3768138

Digital Object Identifier (DOI)

  • 10.1002/path.3987

PubMed ID

  • 22294438

Additional Document Info

start page

  • 53

end page

  • 61

volume

  • 227

number

  • 1