COMMONLY OCCURRING LOSS AND MUTATION OF THE MXII GENE IN PROSTATE-CANCER

One of the most common chromosomal abnormalities in prostate cancer in volves loss of 10q22-qter. Rarely, a smaller deletion, involving 10q2- q25, has been observed, suggesting the presence of a tumor suppressor gene at this site. We previously demonstrated that the MXII gene maps to 10q24-q25 and is mutated in some tumors with cytogenetically detect able deletions of this locus. MXI I encodes a basic-helix-loop-helix p rotein that suppresses the transcriptional activity of the MYC oncopro tein by competing for the common dimerization partner, MAX, and bindin g to identical DNA sites. Because more than 90% of prostate tumors con tain no cytogenetic abnormality of 10q, the relevance of MXII loss and /or mutation to the vast majority of cases remains unclear. We prospec tively evaluated prostate tumors for loss of MXI I by fluorescence in situ hybridization (FISH) and cytogenetic techniques. Twenty-one of 40 tumors (53%) demonstrated loss of a single MX11 allele as determined by FISH. Ten cases with cytogenetically normal 10qs, but with FISH-doc umented deletion of MX11, were examined at the molecular level, and ei ght mutations were identified, albeit at low frequency. Five of the mu tant proteins were unable to bind DNA in association with MAX. We conc lude that MX11 gene loss in prostate cancer is common and most frequen tly involves a cytogenetically undetectable deletion. (C) 1998 Wiley-L iss, Inc.