The expression profile for the tumour suppressor gene PTEN and associated polymorphic markers

PTEN, a putative tumour suppressor gene associated with prostate and other cancers, is known to be located within the chromosomal region 10q23.3. Tran scription of the PTEN gives rise to multiple mRNA species. Analyses by Nort hern blots, using cell lines which express PTEN together with cell lines wh ich have lost the PTEN or carry a truncated version of the gene, has allowe d us to demonstrate that the pseudogene is not transcribed. In addition, 3' RACE studies confirmed that the multiple mRNA species arising from the gen e probably result from the use of alternative polyadenylation sites. No evi dence for tissue- or cell-specific patterns of transcription was found. Ana lysis by 5' RACE placed the putative site for the start of transcription ar ound 830 bp upstream of the start codon. A map of the location of the PTEN gene with a series of overlapping YAC, BAC and PACs has been constructed ac id the relative position of eight microsatellite markers sited. Two known a nd one novel marker have been positioned within the gene, the others are in flanking regions. The more accurate location of these markers should help in future studies of the extent of gene loss. Several polymorphisms were al so identified, all were within introns. Four of the common polymorphisms ap pear to be linked. In blood, DNA from 200 individuals, including normal, BP H and prostate cancer patients, confirmed this link. Only two samples of 20 0 did not carry the linked haplotype, both were patients with advanced pros tate cancer. It is possible that such rearrangements within PTEN could be e vidence of predisposition to prostate cancer in this small number of cases. (C) 2000 Cancer Research Campaign.