TMPRSS2 Gene Rearrangement in Non-Prostatic Epithelial Tumors
C Zanardi, J Tull, S Zhang, C Fuller. SUNY Upstate Medical University, Syracuse, NY
Background: Transmembrane serine protease 2 (TMPRSS2) is an androgen-regulated member of the type two transmembrane protease family (TTSP) that is normally expressed to a variable degree in prostate, colon, stomach, liver, testicle, kidney and pancreas. The TMPRSS2 (21q22.3) gene has been recently observed to be fused with several of the ETS-transcription factor family members, including ERG (21q22.2), ETV1 (7q21.2) or ETV4 (17q21), in a significant percentage of prostate carcinomas. The current study was undertaken to determine whether TMPRSS2 gene rearrangements are detectable in other common non-prostatic epithelial tumors.
Design: Tissue microarrays (TMA) were constructed to contain duplicate or triplicate cores of 164 cases of a variety of carcinomas from the following sites: breast, head and neck region including thyroid and salivary gland, lung, pleura, liver, pancreas, skin, adrenal gland, and gastrointestinal, gynecological, and urogenital systems. These TMAs were then subjected to direct fluorescence in situ hybridization (FISH) using a bacterial artificial chromosome (BAC)-derived TMPRSS2 gene dual-color break-apart probe cocktail. A positive result was reported when greater than 10% of the tumor nuclei had evidence of split red and green signals, indicative of TMPRSS2 gene rearrangement. A parallel analysis of TMAs containing prostate carcinomas was used for comparison.
Results: All tested non-prostatic epithelial tumor cases showed very rare or no tumor cell nuclei with split FISH signals, confirming an intact TMPRSS2 gene region in these tumors. In contradistinction, 62% of tested prostate carcinomas harbored demonstrable TMPRSS2 gene rearrangements.
Conclusions: These findings demonstrate absence of TMPRSS2 gene rearrangements in an extensive sampling of non-prostatic epithelial tumors, supporting the concept that TMPRSS2 alterations are unique and specific to carcinomas of prostatic origin. More comprehensive screening of similar large cohorts of epithelial tumors will be necessary to determine the incidence of rearrangements of ETS family members involving alternate fusion partner genes or other novel gene rearrangements in non-prostatic epithelial tumors.
Category: Special Category for 2009 - Pan-genomic/Pan-proteomic approaches to Cancer
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 240, Tuesday Morning