The loss o r mutational inactivation of the RBI tumor suppressor gene has been implicated in the development of a diverse group of human malignancies. However, the contribution of the RBI gene alteration t o human prostatic carcinogenesis has been poorly understood. Thus far, deletion of the promoter sequence and exon 21 from one primary tumor specimen and the alterations found in the cell line DU-145, are the only cases of RBI mutations reported in human carcinoma of the prostate. This study was designed t o determine whether alterations in the structure or expression of the RBI gene occur in human prostate carcinoma, and to determine the nature of these changes and the frequency with which they occur. One hundred twelve primary prostate tumor tissues and four metastatic lesions were obtained immediately after surgical resection. The RBI gene was characterized in 68 tumor DNA samples using Southern analysis and the PG3.8M or H3-8 probes. Band profiles were analyzed by scanning densitometry. Sixty-three tumor DNA samples were analyzed for defects in the RBI promoter using polymerase chain reaction (PCR) and heteroduplex analysis. Alterations in the expression of exons 1-27 were analyzed in 79 primary and four metastatic tumor RNAs using RT-PCR. Three of 68 tumors were identified to have gross rearrangement of the RBI gene or deletion of one allele. One of four stage D tumor specimens showed truncated RT-PCR products indicating an internal deletion of RBI transcripts. In all, 14 of 83 (17%) specimens displayed abnormally low levels of RBI mRNA expression. Furthermore, these alterations of RBI expression showed a correlation with increasing tumor stage and grade.
These results suggest alterations of RB I mRNA expression occur more frequently in higher stages and grades of prostate cancer and, thus, may be contributing t o the malignant progression of a subset of human prostate cancer. Genes Chromosom Cancer