Co-first authors.
1096-9896/asset/PATH_left.gif?v=1&s=f8845e760fcc5be3e3baa6119dcc01c077e3db22)
1096-9896/asset/PATH_right.gif?v=1&s=86062495907b9532cd169b5a6605dac7fd14f581)
Original Paper
Integrated genome and transcriptome sequencing identifies a novel form of hybrid and aggressive prostate cancer†‡
Article first published online: 21 MAR 2012
DOI: 10.1002/path.3987
Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Additional Information
How to Cite
Wu, C., Wyatt, A. W., Lapuk, A. V., McPherson, A., McConeghy, B. J., Bell, R. H., Anderson, S., Haegert, A., Brahmbhatt, S., Shukin, R., Mo, F., Li, E., Fazli, L., Hurtado-Coll, A., Jones, E. C., Butterfield, Y. S., Hach, F., Hormozdiari, F., Hajirasouliha, I., Boutros, P. C., Bristow, R. G., Jones, S. J., Hirst, M., Marra, M. A., Maher, C. A., Chinnaiyan, A. M., Sahinalp, S. C., Gleave, M. E., Volik, S. V. and Collins, C. C. (2012), Integrated genome and transcriptome sequencing identifies a novel form of hybrid and aggressive prostate cancer. J. Pathol., 227: 53–61. doi: 10.1002/path.3987
- †
Illumina sequence data are available from the Vancouver Prostate Centre web-site at: http://www.lagapc.ca/FTP_HybridPCa.html; aCGH data are available at NCBI GEO, Accession No. GSE34649.
- ‡
No conflicts of interest were declared.
- §
Co-first authors.
Publication History
- Issue published online: 4 APR 2012
- Article first published online: 21 MAR 2012
- Accepted manuscript online: 4 JAN 2012 07:35AM EST
- Manuscript Accepted: 29 DEC 2011
- Manuscript Revised: 23 DEC 2011
- Manuscript Received: 9 DEC 2011
Keywords:
- RNA sequencing;
- DNA sequencing;
- prostate cancer;
- fusion genes;
- neuroendocrine;
- personalized medicine;
- cancer genetics
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.