TMPRSS2-ERG Gene Fusion Causing ERG Overexpression Precedes Chromosome Copy Number Changes in Prostate Carcinomas, Paired HGPIN Lesions

• DOI: 10.1593/neo.06427
• Publication Date: 2006-10-07T10:02:35Z
• Authors: Nuno Cerveira; Franclim R. Ribeiro; Ana Peixoto; Vera Costa; Rui Henrique; Carmen Jerönimo; Manuel R. Teixeira
• Keywords: TMPRSS2; Erg; Comparative genomic hybridization; Chromoplexy

TMPRSS2-ETS gene fusions have been found recurrently in prostate carcinomas, but not the presumed precursor lesion, high-grade prostatic intraepithelial neoplasia (HGPIN). However, HGPIN lesions may share chromosomal changes with cancer. To determine relative order of genetic events carcinogenesis, we analyzed 34 19 paired lesions, 14 benign hyperplasias, 11 morphologically normal tissues for TMPRSS2-ERG, TMPRSS2-ETV1 rearrangements, genomic imbalances. TMPRSS2 exon 1 was fused in-frame ERG 4 17 (50%) (21%) none controls. The findings were further validated by sequencing analysis, real-time polymerase chain reaction quantification TMPRSS2-ERG fusion transcript, exons 5/6:exons 1/2 expression ratio. Chromosome copy number detected comparative hybridization 42% clinically confined 16 analyzed. We demonstrate first time that can be a proportion this molecular rearrangement is an early event precede chromosome-level alterations carcinogenesis.