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From sequence to molecular pathology, and a mechanism driving the neuroendocrine phenotype in prostate cancer
The Journal of pathology, 2012-07, Vol.227 (3), p.286-297
Lapuk, Anna V
Wu, Chunxiao
Wyatt, Alexander W
McPherson, Andrew
McConeghy, Brian J
Brahmbhatt, Sonal
Mo, Fan
Zoubeidi, Amina
Anderson, Shawn
Bell, Robert H
Haegert, Anne
Shukin, Robert
Wang, Yuzhuo
Fazli, Ladan
Hurtado-Coll, Antonio
Jones, Edward C
Hach, Faraz
Hormozdiari, Fereydoun
Hajirasouliha, Iman
Boutros, Paul C
Bristow, Robert G
Zhao, Yongjun
Marra, Marco A
Fanjul, Andrea
Maher, Christopher A
Chinnaiyan, Arul M
Rubin, Mark A
Beltran, Himisha
Sahinalp, S Cenk
Gleave, Martin E
Volik, Stanislav V
Collins, Colin C
2012
Volltextzugriff (PDF)
Details
Autor(en) / Beteiligte
Lapuk, Anna V
Wu, Chunxiao
Wyatt, Alexander W
McPherson, Andrew
McConeghy, Brian J
Brahmbhatt, Sonal
Mo, Fan
Zoubeidi, Amina
Anderson, Shawn
Bell, Robert H
Haegert, Anne
Shukin, Robert
Wang, Yuzhuo
Fazli, Ladan
Hurtado-Coll, Antonio
Jones, Edward C
Hach, Faraz
Hormozdiari, Fereydoun
Hajirasouliha, Iman
Boutros, Paul C
Bristow, Robert G
Zhao, Yongjun
Marra, Marco A
Fanjul, Andrea
Maher, Christopher A
Chinnaiyan, Arul M
Rubin, Mark A
Beltran, Himisha
Sahinalp, S Cenk
Gleave, Martin E
Volik, Stanislav V
Collins, Colin C
Titel
From sequence to molecular pathology, and a mechanism driving the neuroendocrine phenotype in prostate cancer
Ist Teil von
The Journal of pathology, 2012-07, Vol.227 (3), p.286-297
Ort / Verlag
Chichester, UK: John Wiley & Sons, Ltd
Erscheinungsjahr
2012
Quelle
Wiley Online Library Journals Frontfile Complete
Beschreibungen/Notizen
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 aetiology and gene expression profiles; and show the 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.
Sprache
Englisch
Identifikatoren
ISSN: 0022-3417
eISSN: 1096-9896
DOI: 10.1002/path.4047
Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3659819
Format
–
Schlagworte
Adenocarcinoma - genetics
,
Adenocarcinoma - metabolism
,
Adenocarcinoma - secondary
,
Adenocarcinoma - therapy
,
Aged
,
Alternative Splicing
,
Biological and medical sciences
,
Biomarkers, Tumor - blood
,
Biomarkers, Tumor - genetics
,
British Columbia
,
Cell Line, Tumor
,
Cell Transformation, Neoplastic - genetics
,
Cell Transformation, Neoplastic - metabolism
,
Cell Transformation, Neoplastic - pathology
,
chromothripsis
,
Cluster Analysis
,
Decision Support Techniques
,
Gene Dosage
,
Gene Expression Profiling - methods
,
Gene Expression Regulation, Neoplastic
,
Gene Fusion
,
Genetic Predisposition to Disease
,
Gynecology. Andrology. Obstetrics
,
Humans
,
Investigative techniques, diagnostic techniques (general aspects)
,
Lymphatic Metastasis
,
Male
,
Male genital diseases
,
massively parallel sequencing
,
Medical sciences
,
Middle Aged
,
molecular pathology
,
Neoplasm Grading
,
Neoplasms, Hormone-Dependent - genetics
,
Neoplasms, Hormone-Dependent - metabolism
,
Neoplasms, Hormone-Dependent - pathology
,
Neoplasms, Hormone-Dependent - therapy
,
Nephrology. Urinary tract diseases
,
Neuroendocrine Cells - metabolism
,
Neuroendocrine Cells - pathology
,
neuroendocrine prostate cancer
,
Nomograms
,
Oligonucleotide Array Sequence Analysis
,
Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques
,
Patient Selection
,
Phenotype
,
Precision Medicine
,
Prognosis
,
Prostate-Specific Antigen - blood
,
Prostatic Neoplasms - genetics
,
Prostatic Neoplasms - metabolism
,
Prostatic Neoplasms - pathology
,
Prostatic Neoplasms - therapy
,
REST repressor
,
RNA Interference
,
Transfection
,
Tumors
,
Tumors of the urinary system
,
Urinary tract. Prostate gland
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