A novel germline mutation of PTEN associated with brain tumours of multiple lineages
| Autor: | J van Drunen, H van Bakel, B Burgering, Frank J. T. Staal, M J B Taphoorn, R. B. van der Luijt, I de Valk, E. D. J. Peters, M R M Baert, C.W.M. van Veelen, Gerard E.J. Staal, Gerard H. Jansen, H. K. P. Van Amstel |
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| Přispěvatelé: | Immunology |
| Rok vydání: | 2002 |
| Předmět: |
Male
Models Molecular PTEN Cancer Research Protein Conformation DNA Mutational Analysis Loss of Heterozygosity Apoptosis medicine.disease_cause Germline Neoplasms Multiple Primary Loss of heterozygosity glioma Meningeal Neoplasms Insulin Missense mutation PKB Mutation Brain Neoplasms DNA Neoplasm U937 Cells tumour suppressor gene Frontal Lobe Neoplasm Proteins Oncology Meningioma Cell Division Adult Tumor suppressor gene Oligodendroglioma Mutation Missense Protein Serine-Threonine Kinases Biology Transfection Germline mutation Proto-Oncogene Proteins medicine Humans Point Mutation Cell Lineage Genetic Predisposition to Disease Germ-Line Mutation Akt Tumor Suppressor Proteins Point mutation PTEN Phosphohydrolase Genetics and Genomics Phosphoric Monoester Hydrolases Enzyme Activation Amino Acid Substitution Cancer research biology.protein Proto-Oncogene Proteins c-akt |
| Zdroj: | British Journal of Cancer, 86, 1586-1591. Nature Publishing Group British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/sj.bjc.6600206 |
| Popis: | We have identified a novel germline mutation in the PTEN tumour suppressor gene. The mutation was identified in a patient with a glioma, and turned out to be a heterozygous germline mutation of PTEN (Arg234Gln), without loss of heterozygosity in tumour DNA. The biological consequences of this germline mutation were investigated by means of transfection studies of the mutant PTEN molecule compared to wild-type PTEN. In contrast to the wild-type molecule, the mutant PTEN protein is not capable of inducing apoptosis, induces increased cell proliferation and leads to high constitutive PKB/Akt activation, which cannot be increased anymore by stimulation with insulin. The reported patient, in addition to glioma, had suffered from benign meningioma in the past but did not show any clinical signs of Cowden disease or other hereditary diseases typically associated with PTEN germline mutations. The functional consequences of the mutation in transfection studies are consistent with high proliferative activity. Together, these findings suggest that the Arg234Gln missense mutation in PTEN has oncogenic properties and predisposes to brain tumours of multiple lineages. British Journal of Cancer (2002) 86, 1586–1591. DOI: 10.1038/sj/bjc/6600206 www.bjcancer.com © 2002 Cancer Research UK |
| Databáze: | OpenAIRE |
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