title: PTEN/MMAC1 is infrequently mutated in pT2 and pT3 carcinomas of the prostate.
abstract: Deletion of the q23-24 region of human chromosome 10 is one of the most frequent genetic alterations in prostate cancer, suggesting that inactivation of a tumor suppressor gene in this region is involved in the development or progression of this carcinoma. A candidate gene, PTEN/MMAC1, has been identified from this chromosomal region; mutations of this gene have been found in various advanced tumors and cell lines including those of prostate cancer. To further define the role of PTEN/MMAC1 in the development of prostate cancer and its spectrum of genetic alterations, we analysed 40 pT2 or pT3 prostate tumors for allelic loss, mutations, and homozygous deletions using PCR-based methods. Six tumors showed loss of heterozygosity for one of the ten markers analysed, while one tumor showed loss of two markers. None of the markers within PTEN/MMAC1 was lost. Direct sequencing of PCR amplified exons and intron/exon junctions of all 40 tumors revealed three sequence variants, one of which was a point mutation in exon 9, while the other two were polymorphisms. Using multiplex PCR, no homozygous deletions were detected in any of the neoplasms. Our results showing a low frequency of alterations of PTEN/MMAC1 in pT2 and pT3 prostate cancers suggest that this gene plays an insignificant role in the development of most low stage carcinomas of the prostate.
authors.affiliation: Department of Pathology, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
authors.forename: J T
authors.initials: JT
authors.lastname: Dong
authors.forename: T W
authors.initials: TW
authors.lastname: Sipe
authors.forename: E R
authors.initials: ER
authors.lastname: Hyytinen
authors.forename: C L
authors.initials: CL
authors.lastname: Li
authors.forename: C
authors.initials: C
authors.lastname: Heise
authors.forename: D E
authors.initials: DE
authors.lastname: McClintock
authors.forename: C D
authors.initials: CD
authors.lastname: Grant
authors.forename: L W
authors.initials: LW
authors.lastname: Chung
authors.forename: H F
authors.initials: HF
authors.lastname: Frierson
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D017931:DNA Primers; D016147:Genes, Tumor Suppressor; D006720:Homozygote; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009154:Mutation; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D017384:Sequence Deletion; D025521:Tumor Suppressor Proteins
chemical_list: D017931:DNA Primers; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D017027:Protein Tyrosine Phosphatases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human