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Integrated genome and transcriptome sequencing identifies a novel form of hybrid and aggressive prostate cancer
Author(s) -
Wu Chunxiao,
Wyatt Alexander W,
Lapuk Anna V,
McPherson Andrew,
McConeghy Brian J,
Bell Robert H,
Anderson Shawn,
Haegert Anne,
Brahmbhatt Sonal,
Shukin Robert,
Mo Fan,
Li Estelle,
Fazli Ladan,
HurtadoColl Antonio,
Jones Edward C,
Butterfield Yaron S,
Hach Faraz,
Hormozdiari Fereydoun,
Hajirasouliha Iman,
Boutros Paul C,
Bristow Robert G,
Jones Steven JM,
Hirst Martin,
Marra Marco A,
Maher Christopher A,
Chinnaiyan Arul M,
Sahinalp S Cenk,
Gleave Martin E,
Volik Stanislav V,
Collins Colin C
Publication year - 2012
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.3987
Subject(s) - transcriptome , biology , prostate cancer , chromoplexy , gene , genome , exome , computational biology , cancer , exome sequencing , cancer research , genetics , mutation , gene expression , pca3
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.