Journal Article

PTEN/MMAC1 is infrequently mutated in pT2 and pT3 carcinomas of the prostate

Sipe, Tavis W, Hyytinen, Eija-Riitta, Li, Chang-Ling, Heise, Christopher, Dong, Jin-Tang, Chung, Leland WK, Frierson, Henry F, McClintock, Dana E, Grant, Charles D

1998

Overview

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.

• Publisher: Nature Publishing,Nature Publishing Group
• Subject: Adult / Aged / Base Sequence / Biological and medical sciences / Cell physiology / Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes / Chromosome 10 / Chromosome deletion / DNA Primers / Exons / Fundamental and applied biological sciences. Psychology / Genes, Tumor Suppressor / Genetic analysis / Gynecology. Andrology. Obstetrics / Heterozygosity / Homozygote / Humans / Loss of Heterozygosity / Male / Male genital diseases / Medical sciences / Middle Aged / Molecular and cellular biology / Mutation / Phosphoric Monoester Hydrolases / Point mutation / Prostate cancer / Prostate carcinoma / Prostatic Neoplasms - genetics / Prostatic Neoplasms - pathology / Protein Tyrosine Phosphatases - genetics / PTEN Phosphohydrolase / PTEN protein / Sequence Deletion / Tumor suppressor genes / Tumor Suppressor Proteins / Tumors