Heterogeneity of TMPRSS2 gene rearrangements in multifocal prostate adenocarcinoma: molecular evidence for an independent group of diseases.

Heterogeneity of TMPRSS2 gene rearrangements in multifocal prostate adenocarcinoma: molecular evidence for an independent group of diseases. Research Abstract Details 

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Heterogeneity of TMPRSS2 gene rearrangements in multifocal prostate adenocarcinoma: molecular evidence for an independent group of diseases. Abstract Text:

Rohit Mehra,Bo Han,Scott A Tomlins,Lei Wang,Anjana Menon,Matthew J Wasco,Ronglai Shen,James E Montie,Arul M Chinnaiyan,Rajal B Shah,

Recurrent gene fusions between the androgen-regulated gene TMPRSS2 and the ETS family transcription factors ERG, ETV1, and ETV4 have been identified in the majority of prostate adenocarcinomas (PCA). PCA is often multifocal with histologic heterogeneity of different tumor foci. As TMPRSS2 is a common 5' partner of ETS gene fusions, we monitored TMPRSS2 rearrangement by fluorescence in situ hybridization (FISH) to study the origin and molecular basis of multifocal PCA heterogeneity. TMPRSS2 rearrangement was evaluated by FISH on a tissue microarray representing 93 multifocal PCAs from 43 radical prostatectomy resections. Overall, 70% (30 of 43) of the cases showed TMPRSS2 rearrangement, including 63% through deletion (loss of the 3' TMPRSS2 signal), 27% through translocation (split of 5' and 3' TMPRSS2 signals), and 10% through both mechanisms in different tumor foci. Of the 30 TMPRSS2 rearranged cases, 30% showed concordance in all tumor foci, whereas 70% were discordant in at least one focus. In TMPRSS2 rearranged cases, the largest (index) tumor was rearranged 83% of the time. Pathologic stage, size, or Gleason grade of the multifocal PCA did not correlate with overall TMPRSS2 rearrangement. Our results suggest that multifocal PCA is a heterogeneous group of diseases arising from multiple, independent clonal expansions. Understanding this molecular heterogeneity is critical to the future development and utility of diagnostic and prognostic PCA biomarkers.

Heterogeneity of TMPRSS2 gene rearrangements in multifocal prostate adenocarcinoma: molecular evidence for an independent group of diseases. Publishing Authors By Initials

R Mehra,B Han,SA Tomlins,L Wang,A Menon,MJ Wasco,R Shen,JE Montie,AM Chinnaiyan,RB Shah,

For similar pathological conditions, signs and symptoms: pathologic processes: chromosome aberrations: translocation, genetic research abstracts see: pathological conditions, signs and symptoms: pathologic processes: chromosome aberrations: translocation, genetic research

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Heterogeneity of TMPRSS2 gene rearrangements in multifocal prostate adenocarcinoma: molecular evidence for an independent group of diseases. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Cancer research

VOLUME: 67

Page Numbers: 7991-5

Journal Abbreviation: Cancer Res.

ISSN: 0008-5472

DAY: 1

MONTH: Sep

YEAR: 2007

Heterogeneity of TMPRSS2 gene rearrangements in multifocal prostate adenocarcinoma: molecular evidence for an independent group of diseases. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2984705

Heterogeneity of TMPRSS2 gene rearrangements in multifocal prostate adenocarcinoma: molecular evidence for an independent group of diseases. Keywords Mesh Terms:

KEYWORDS: Translocation, Genetic

MESH TERMS: genetics

Chemical & Substance for Abstract: Heterogeneity of TMPRSS2 gene rearrangements in multifocal prostate adenocarcinoma: molecular evidence for an independent group of diseases. Information

Substance Name: TMPRSS2 protein, human

Registry Number: EC 3.4.21.-

Grant and Affiliation Information for Heterogeneity of TMPRSS2 gene rearrangements in multifocal prostate adenocarcinoma: molecular evidence for an independent group of diseases.

AFFILIATION: Michigan Center for Translational Pathology, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

Country: United States

AGENCY: United States NCI

GRANT: U01 CA111275-01

ACRONYM: CA

MEDLINETA: Cancer Res

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