ALLELIC IMBALANCE AND MICROSATELLITE INSTABILITY IN PROSTATIC ADENOCARCINOMA

Although prostate cancer is one of the most common malignancies of mal es in Western countries, relatively little is known about the molecula r mechanisms involved in tumor initiation and progression. Allelic los s studies have suggested the involvement of multiple tumor suppressor genes (TSGs), but few detailed studies of all chromosomes have been pe rformed. In an effort to localize and identify candidate TSGs, we perf ormed allelic imbalance (AI) studies on 55 prostate cancers, using 135 polymorphic microsatellite markers. For the entire chromosome, AI ran ged from a low of 0% on chromosomes 14 and 20 to a high of 71% on chro mosome 8. Chromosomal regions demonstrating at least twice the backgro und frequency of AI (ranging from 20 to 69%) included 5q, 6q, 7q, 8p, 13, 16q, 18q, and 21. In addition, AI was examined for association wit h a number of clinicopathological parameters. AI on chromosomes 7 and 16 were each associated with greater age at diagnosis (P = 0.009 and 0 .001, respectively), and AI on chromosomes 10, 16, and 18 was associat ed with aneuploidy/tetraploidy (P = 0.037, 0.013, and 0.054, respectiv ely). Furthermore, AI on chromosome 5 was associated with a higher pat hological stage (P = 0.021) and on chromosome 8 and 16 with a higher G leason score (P = 0.027 and 0.041, respectively). No tumor exhibited a phenotype of widespread microsatellite instability. These results ind icate that there likely exist multiple sites harboring candidate TSG i n prostate cancer, some of which may have important clinical implicati ons, and which argue against widespread microsatellite instability.