Integrated genome and transcriptome sequencing identifies a novel form of hybrid and aggressive prostate cancer

Chunxiao Wu, Alexander W. Wyatt, Anna V. Lapuk, Andrew McPherson, Brian J. McConeghy, Robert H. Bell, Shawn Anderson, Anne Haegert, Sonal Brahmbhatt, Robert Shukin, Fan Mo, Estelle Li, Ladan Fazli, Antonio Hurtado-Coll, Edward C. Jones, Yaron S. Butterfield, Faraz Hach, Fereydoun Hormozdiari, Iman Hajirasouliha, Paul C. BoutrosRobert G. Bristow, Steven J.M. Jones, Martin Hirst, Marco A. Marra, Christopher A. Maher, Arul M. Chinnaiyan, S. Cenk Sahinalp, Martin E. Gleave, Stanislav V. Volik, Colin C. Collins

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)53-61
Number of pages9
JournalJournal of Pathology
Volume227
Issue number1
DOIs
StatePublished - Jan 1 2012
Externally publishedYes

Keywords

  • Cancer genetics
  • DNA sequencing
  • Fusion genes
  • Neuroendocrine
  • Personalized medicine
  • Prostate cancer
  • RNA sequencing

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint Dive into the research topics of 'Integrated genome and transcriptome sequencing identifies a novel form of hybrid and aggressive prostate cancer'. Together they form a unique fingerprint.

Cite this