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.
Written by:
Wu C, Wyatt AW, Lapuk AV, McPherson A, McConeghy BJ, Bell RH, Anderson S, Haegert A, Brahmbhatt S, Shukin R, Mo F, Li E, Fazli L, Hurtado-Coll A, Jones EC, Butterfield YS, Hach F, Hormozdiari F, Hajirasouliha I, Boutros PC, Bristow RG, Jones SJ, Hirst M, Marra MA, Maher CA, Chinnaiyan AM, Sahinalp SC, Gleave ME, Volik SV, Collins CC. Are you the author?
Vancouver Prostate Centre and Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
Reference: J Pathol. 2012 May;227(1):53-61.
doi: 10.1002/path.3987. Epub 2012 Mar 21.
PubMed Abstract
PMID: 22294438
UroToday.com Investigational Urology Section
