Differential chromosome allelic imbalance in the progression of human prostate cancer.

Abstract

It is widely accepted that an accumulation of genetic alterations plays an important role in the genesis of human cancers. We wished to obtain a comprehensive view of the role of genetic changes in prostate cancer. We screened 42 primary prostate tumors for allelic imbalance (AI) on 8 autosomal chromosome arms of interest (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). The most frequent allelic imbalances were observed on 8p (58%) and 16q (53%). AI exceeding 20% was also observed at sites on chromosome arms 7q (46%), 10q (23%), 13q (26%), 17q (34%) and 18q (39%), whereas AI was infrequent on 5q (10%). The data indicate that a relatively large number of chromosome loci play a part in the etiology and progression of this tumor type. Moreover, our findings suggest that inactivation of a putative tumor suppressor 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 and 18q suggests that these genetic alterations occur late in prostate tumorigenesis.