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. Transcription of the PTEN gives rise to multiple mRNA species. Analyses by Northern blots, using cell lines which express PTEN together with cell lines which have lost the PTEN or carry a truncated version of the gene, has allowed us to demonstrate that the pseudogene is not transcribed. In addition, 3' RACE studies confirmed that the multiple mRNA species arising from the gene probably result from the use of alternative polyadenylation sites. No evidence for tissue- or cell-specific patterns of transcription was found. Analysis by 5' RACE placed the putative site for the start of transcription around 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 and the relative position of eight microsatellite markers sited. Two known and 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 also identified, all were within introns. Four of the common polymorphisms appear to be linked. In blood, DNA from 200 individuals, including normal, BPH and prostate cancer patients, confirmed this link. Only two samples of 200 did not carry the linked haplotype, both were patients with advanced prostate cancer. It is possible that such rearrangements within PTEN could be evidence of predisposition to prostate cancer in this small number of cases.
Hamilton
J A
JA
Applied Development Laboratory, Imperial Cancer Research Fund, Dominion House, St Bartholomew's Hospital, London, UK.
Stewart
L M
LM
Ajayi
L
L
Gray
I C
IC
Gray
N E
NE
Roberts
K G
KG
Watson
G J
GJ
Kaisary
A V
AV
Snary
D
D
D017398:Alternative Splicing; D015152:Blotting, Northern; D002874:Chromosome Mapping / Q000379:methods; D018244:Chromosomes, Artificial, Yeast / Q000235:genetics; D002876:Chromosomes, Bacterial / Q000235:genetics; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D005819:Genetic Markers; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats / Q000235:genetics; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000235:genetics; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D005819:Genetic Markers; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human