Analysis of PTEN and the 10q23 region in primary prostate carcinomas.
Deletions involving chromosome 10q23 occur frequently in prostatic carcinomas. Recently, a novel tumour suppressor gene, PTEN, mapping to this interval, has been identified. Mutation or deletion of PTEN has been observed in a proportion of prostate cancer cell lines; however, primary prostate carcinomas have not been studied. We have investigated the involvement of PTEN in primary prostatic adenocarcinomas using a panel of 51 matched normal and prostate tumour DNAs. We first determined the proportion of tumours with allele loss at loci in 10q23 which span the region containing the PTEN gene. Our results show that LOH involving 10q23 is common in primary prostate carcinomas. Twenty-five of 51 (49%) tumours showed loss of heterozygosity (LOH) over the region spanning the PTEN locus. We next directly analysed the PTEN gene for mutations of the coding region using single strand conformation polymorphism (SSCP) and sequence analyses. Of those tumours with LOH, only a single tumour was found to carry a missense mutation in PTEN. No mutations in PTEN were identified in tumours without LOH. Our results suggest either that mutation of PTEN is a late event in prostate tumorigenesis, or that another tumour suppressor gene important in prostate cancer may lie close to PTEN in 10q23.
Feilotter
H E
HE
Department of Pathology, Queen's University, Kingston, Ontario, Canada.
Nagai
M A
MA
Boag
A H
AH
Eng
C
C
Mulligan
L M
LM
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D002879:Chromosomes, Human, Pair 10; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D025521:Tumor Suppressor Proteins
D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D017027:Protein Tyrosine Phosphatases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human