From sequence to molecular pathology, and a mechanism driving the neuroendocrine phenotype in prostate cancer.
Summary of "From sequence to molecular pathology, and a mechanism driving the neuroendocrine phenotype in prostate cancer."
The current paradigm of cancer care relies on predictive nomograms which integrate detailed histopathology with clinical data. However, when predictions fail, the consequences for patients are often catastrophic, especially in prostate cancer where nomograms influence the decision to therapeutically intervene. We hypothesized that the high dimensional data afforded by massively-parallel sequencing (MPS) is not only capable of providing biological insights, but may aid molecular pathology of prostate tumours. We assembled a cohort of six patients with high-risk disease, and performed deep RNA and shallow DNA sequencing in primary tumours and matched metastases where available. Our analysis identified copy number abnormalities, accurately profiled gene expression levels, and detected both differential splicing and expressed fusion genes. We revealed occult and potentially dormant metastases, unambiguously supporting the patients' clinical history; and implicated the REST transcriptional complex in the development of neuroendocrine prostate cancer, validating this finding in a large independent cohort. We massively expand on the number of novel fusion genes described in prostate cancer, provide fresh evidence for the growing link between fusion gene etiology and gene expression profiles and show utility of fusion genes for molecular pathology. Finally we identified chromothripsis in a patient with chronic prostatitis. Our results provide a strong foundation for further development of MPS-based molecular pathology. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Affiliation
Vancouver Prostate Centre & Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
Journal Details
This article was published in the following journal.
Name: The Journal of pathology
ISSN: 1096-9896
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22553170
- DOI: http://dx.doi.org/10.1002/path.4047
Medical and Biotech [MESH] Definitions
Automobile Driving
The effect of environmental or physiological factors on the driver and driving ability. Included are driving fatigue, and the effect of drugs, disease, and physical disabilities on driving.
Pathology, Molecular
A subspecialty of pathology concerned with the molecular basis (e.g., mutations) of various diseases.
Molecular Sequence Annotation
The addition of descriptive information about the function or structure of a molecular sequence to its MOLECULAR SEQUENCE DATA record.
Neuroendocrine Secretory Protein 7b2
An acidic protein found in the NEUROENDOCRINE SYSTEM that functions as a molecular chaperone for PROPROTEIN CONVERTASE 2.
Molecular Sequence Data
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
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