Abstract |
Mutations in the PTEN gene are frequent in endometrial carcinoma. PTEN methylation is an alternative mechanism of gene inactivation. To elucidate different mechanisms of PTEN gene inactivation, we have studied a population-based series of endometrial carcinomas for PTEN mutations in relation to clinicopathologic characteristics, promoter methylation and protein expression. PTEN mutations were found in 54%, mainly in exons 5 and 8; with at least two different mutations in 21%. Presence of PTEN mutation was significantly correlated with young age, low FIGO-stage, endometrioid subtype, low grade, microsatellite instability and favourable prognosis. Previous studies of these tumours have observed PTEN methylation in 18% and low protein expression in 20%. Low expression of PTEN-antibody 6H2.1 was correlated with the presence of mutations in exon 8 among patients with 'two hits'; i.e. > or =2 mutations, or mutation(s) plus methylation (p=0.001). Number of PTEN hits was significantly associated with microsatellite instability, low hMLH1 expression and hMLH1 methylation. Thus, PTEN mutations are frequent in sporadic endometrial carcinoma and define a prognostically favourable subgroup, whereas the relationship with PTEN protein expression is complex. A pathway in endometrial carcinogenesis involving PTEN mutation and microsatellite instability is confirmed, and this study also indicates the importance of PTEN and hMLH1 methylation in this pathway.
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Authors | Helga B Salvesen, Ingunn Stefansson, Ellen I Kretzschmar, Paula Gruber, Nicola D MacDonald, Andy Ryan, Ian J Jacobs, Lars A Akslen, Soma Das |
Journal | International journal of oncology
(Int J Oncol)
Vol. 25
Issue 6
Pg. 1615-23
(Dec 2004)
ISSN: 1019-6439 [Print] Greece |
PMID | 15547698
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Tumor Suppressor Proteins
- Phosphoric Monoester Hydrolases
- PTEN Phosphohydrolase
- PTEN protein, human
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Topics |
- Adult
- Aged
- Carcinoma
(genetics, pathology)
- DNA Methylation
- DNA Mutational Analysis
- Endometrial Neoplasms
(genetics, pathology)
- Female
- Gene Expression Profiling
- Genes, Tumor Suppressor
- Germ-Line Mutation
- Humans
- Microsatellite Repeats
- Middle Aged
- PTEN Phosphohydrolase
- Phosphoric Monoester Hydrolases
(biosynthesis, genetics)
- Prognosis
- Promoter Regions, Genetic
- Survival Analysis
- Tumor Suppressor Proteins
(biosynthesis, genetics)
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