DIFFERENTIAL CHROMOSOME ALLELIC IMBALANCE IN THE PROGRESSION OF HUMANPROSTATE-CANCER

Purpose: It is widely accepted that an accumulation of genetic alterat ions plays an important role in the genesis of human cancers. We wishe d to obtain a comprehensive view of the role of genetic changes in pro state cancer. Materials and Methods: We screened 42 primary prostate t umors for allelic imbalance (AI) on 8 autosomal chromosome arms of int erest (5q, 7q, 8p, 10q, 13q, 16q, 17q, 18q) by using 2 DNA probes for restriction fragment length polymorphism (RFLP) and 19 microsatellite markers (CA repeats). Results: The most frequent allelic imbalances we re observed on 8p (58%) and 16q (53%). AI exceeding 20% was also obser ved at sites on chromosome arms 7q (46%), 10q (23%), 13q (26%), 17q (3 4%) and 18q (39%), whereas AI was infrequent on 5q (10%). Conclusions: The data indicate that a relatively large number of chromosome loci p lay a part in the etiology and progression of this tumor type. Moreove r, our findings suggest that inactivation of a putative tumor suppress or gene on 7q and 13q is an early event in prostate tumorigenesis. In contrast, the close link between an invasive phenotype and AI on 10q a nd 18q suggests that these genetic alterations occur late in prostate tumorigenesis.