Identification of 12p as a region of frequent deletion in advanced prostate cancer

The identification of homozygous deletions in malignant tissue has been a p owerful tool for the localization of tumor suppressor genes, Representation al difference analysis (RDA) uses selective hybridization and the PCR to is olate regions of chromosomal loss and has facilitated the identification of tumor suppressor genes such as BRCA2 and PTEN, Twenty RDA clones were gene rated by comparing genomic DNA from a prostate cancer xenograft to the same patient's normal kidney DNA, Southern blot analysis of the tester and driv er and of normal and xenograft DNA, using the differential products as prob es, showed the homozygous deletion in 16 of 20 RDA clones. The sequence of one of the differential products overlapped HSU59962, a genomic GenBank seq uence on chromosome 12p12-13. Multiplex PCR of the xenograft DNA using poly morphic repeats mapped the deletion to a 1-5-cM region on 12p, Genomic DNA isolated from a panel of cryostat microdissected metastatic prostate adenoc arcinomas/normal pairs was screened for loss of heterozygosity using the sa me polymorphic repeats, Loss of heterozygosity was demonstrated in 9 (47%) of 19 patients, This region may contain, or lie in close proximity to, tumo r suppressor genes important in the progression and/or initiation of prosta te cancer.