Testing mutual exclusivity of ETS rearranged prostate cancer

Autor: Ubaradka G. Sathyanarayana, Ashley M Santa-Cruz, Karl Garsha, Theresa Y. MacDonald, Naoki Kitabayashi, Mark A. Rubin, Francesca Demichelis, Gary Pestano, Christopher J. LaFargue, Ashutosh K. Tewari, Dea Nagy, Jerry W. Kosmeder, Janice Riley, Chol S Yun, Maria A. Svensson, Dorothee Pflueger
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Male
Pathology
medicine.medical_specialty
TMPRSS2-ERG
Oncogene Proteins
Fusion
Biology
Somatic evolution in cancer
ETV1
Pathology and Forensic Medicine
Fusion gene
Cohort Studies
03 medical and health sciences
Prostate cancer
ETS (E26 transformation specific) rearrangements
0302 clinical medicine
Transcriptional Regulator ERG
Quantum Dots
medicine
Humans
Molecular Biology
In Situ Hybridization
Fluorescence
030304 developmental biology
Aged
Neoplasm Staging
Gene Rearrangement
0303 health sciences
medicine.diagnostic_test
Cancer
Prostatic Neoplasms
Cell Biology
Gene rearrangement
Middle Aged
medicine.disease
prostate cancer
3. Good health
Molecular Imaging
DNA-Binding Proteins
Cell Transformation
Neoplastic
Tissue Array Analysis
030220 oncology & carcinogenesis
Cancer research
Trans-Activators
heterogeneity
Gene Fusion
Fluorescence in situ hybridization
Research Article
Transcription Factors
Zdroj: Laboratory Investigation; a Journal of Technical Methods and Pathology
ISSN: 1530-0307
0023-6837
Popis: Prostate cancer is a clinically heterogeneous and multifocal disease. More than 80% of patients with prostate cancer harbor multiple geographically discrete cancer foci at the time of diagnosis. Emerging data suggest that these foci are molecularly distinct consistent with the hypothesis that they arise as independent clones. One of the strongest arguments is the heterogeneity observed in the status of E26 transformation specific (ETS) rearrangements between discrete tumor foci. The clonal evolution of individual prostate cancer foci based on recent studies demonstrates intertumoral heterogeneity with intratumoral homogeneity. The issue of multifocality and interfocal heterogeneity is important and has not been fully elucidated due to lack of the systematic evaluation of ETS rearrangements in multiple tumor sites. The current study investigates the frequency of multiple gene rearrangements within the same focus and between different cancer foci. Fluorescence in situ hybridization (FISH) assays were designed to detect the four most common recurrent ETS gene rearrangements. In a cohort of 88 men with localized prostate cancer, we found ERG, ETV1, and ETV5 rearrangements in 51% (44/86), 6% (5/85), and 1% (1/86), respectively. None of the cases demonstrated ETV4 rearrangements. Mutual exclusiveness of ETS rearrangements was observed in the majority of cases; however, in six cases, we discovered multiple ETS or 5′ fusion partner rearrangements within the same tumor focus. In conclusion, we provide further evidence for prostate cancer tumor heterogeneity with the identification of multiple concurrent gene rearrangements.
Databáze: OpenAIRE
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