This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hofer, M. D. Articles by Hoegel, J. Search for Related Content PubMed PubMed Citation Articles by Hofer, M. D. Articles by Hoegel, J.

Genome-Wide Linkage Analysis of TMPRSS2-ERG Fusion in Familial Prostate Cancer

¹ Department of Pathology, Brigham and Women's Hospital; ² Harvard Medical School, Boston, Massachusetts; ³ Urologic University Hospital Ulm; ⁴ Institute of Human Genetics and ⁵ Department of Pathology, University Hospital Ulm, Ulm, Germany; and ⁶ Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York

Requests for reprints: Mark A. Rubin, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, 1300 York Avenue, Room C410-A (or Box #69), New York, NY 10021. Phone: 212-746-6313; Fax: 212-746-8816; E-mail: rubinma{at}med.cornell.edu.

Key Words: TMPRSS2 • ERG • HPCX • prostate cancer • familial prostate cancer

Fusion of the 5'-untranslated region of androgen-regulated TMPRSS2 promoter with ETS transcription factor family members is found frequently in prostate cancers, and recent work suggests that the most common TMPRSS2-ERG fusion is associated with an aggressive clinical phenotype compared with fusion-negative prostate cancer. Thus far, analysis of the fusion has been limited to sporadic cases of prostate cancer. In the current study, we explore for an enrichment of TMPRSS2-ERG fusion in familial prostate cancer. TMPRSS2-ERG fusion was identified using a break-apart fluorescence in situ hybridization assay on tissue microarrays. Presence of TMPRSS2-ERG fusion was associated with higher Gleason scores (P = 0.027). Of 75 patients with established history of prostate cancer, we detected the TMPRSS2-ERG fusion in 44 (59%) patients. Almost three quarters (73%) of fusion-positive patients accumulated within 16 specific families whereas only 27% were single fusion-positive cases within one family. Based on reported prevalence rates, we calculated a sibling recurrence risk ratio of up to 18.9. A subset (63%) of families with uniformly TMPRSS2-ERG–positive prostate cancer underwent a genome-wide linkage scan at 500 markers. This revealed several loci located on chromosomes #9, #18, and X that were suggestive of linkage to the TMPRSS2-ERG fusion-positive prostate cancer phenotype with linkage-of-disease scores up to 2.16 and nonparametric linkage scores up to 2.77. This suggests the presence of an inherited susceptibility to developing the TMPRSS2-ERG fusion. Given the association of TMPRSS2-ERG fusion and aggressive prostate cancer, close surveillance of relatives of patients with established fusion-positive prostate cancer or a family history of prostate cancer in general would be warranted. [Cancer Res 2009;69(4):640–6]

This article has been cited by other articles:

				M. Luedeke, C. M. Linnert, M. D. Hofer, H. M. Surowy, A. E. Rinckleb, J. Hoegel, R. Kuefer, M. A. Rubin, W. Vogel, and C. Maier Predisposition for TMPRSS2-ERG Fusion in Prostate Cancer by Variants in DNA Repair Genes Cancer Epidemiol. Biomarkers Prev., November 1, 2009; 18(11): 3030 - 3035. [Abstract] [Full Text] [PDF]