학술논문
A novel germline mutation of PTEN associated with brain tumours of multiple lineages.
Document Type
Journal Article
Author
Source
Subject
*BRAIN tumors
*TUMOR suppressor genes
*GENETIC mutation
*PROTEIN metabolism
*PROTEINS
*FRONTAL lobe
*CELL differentiation
*BIOCHEMISTRY
*DNA
*SEQUENCE analysis
*MATHEMATICAL models
*PHENOMENOLOGICAL biology
*PHOSPHATASES
*GLIOMAS
*APOPTOSIS
*CANCER
*CELL division
*INSULIN
*TRANSFERASES
*MENINGES
*MENINGIOMA
*THEORY
*DISEASE susceptibility
*AMINO acids
*MULTIPLE tumors
*GENETIC techniques
*MOLECULAR structure
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Language
ISSN
0007-0920
Abstract
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. [ABSTRACT FROM AUTHOR]