ORPHA: 182067;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 10q23.31 | {Glioma susceptibility 2} | 613028 | Autosomal dominant | 3 | PTEN | 601728 |
A number sign (#) is used with this entry because glioma may present as part of a tumor predisposition syndrome caused by mutation in the PTEN gene (601728) on chromosome 10q23.
For a general phenotypic description and a discussion of genetic heterogeneity of glioma, see GLM1 (137800).
Staal et al. (2002) identified a heterozygous germline mutation in the PTEN gene in a patient with glioma. A 38-year-old male presented with focal seizures of the right arm and dysphasia. No neurologic abnormalities were found on examination. Antiepileptic drug medication resulted in a marked reduction of the seizures. Several years later a CT brain scan was made because of progressive headaches and memory difficulties. A right frontal meningioma was detected, removed, and pathologically confirmed, with no signs of malignancy. Five years later the seizures had spread to the patient's right leg. A CT scan suggested a low-grade glioma in the left frontal lobe, for which the patient later underwent surgery. Histologic examination revealed tumor cells with perinuclear unstained cytoplasm, with irregular round to oval nuclei, with some mitotic activity. The capillary network in the tumor was unremarkable and there was no necrosis. This tumor was classified as an anaplastic oligodendroglioma. The patient underwent radiotherapy. Several years later the patient suffered a decline of cognitive functioning. CT brain scan showed regrowth of the left frontal tumor, which was again treated surgically. Histologic examination revealed a similar profile to that of the former tumor, but with more pleiomorphism of the nuclei of the tumor cells, more mitotic activity, microvascular proliferation, and small areas of necrosis. The diagnosis was anaplastic oligodendroglioma with signs of ongoing dedifferentiation. He was treated with chemotherapy for residual tumor, but after nearly a year there was further tumor growth.
In a patient with glioma and meningioma, Staal et al. (2002) detected a heterozygous arg234-to-gln (R234Q) mutation in exon 7 of the PTEN gene (601728.0029). The mutation was found in DNA obtained from peripheral blood, the meningioma, and the 2 oligodendrogliomas of the patient, and was not found in 80 control chromosomes. No LOH was detected in tumor-derived DNA samples. In cell proliferation analyses, mutant cells proliferated at a roughly 5-fold higher rate than cells transfected with wildtype PTEN over a 2-week period. Transfection assays showed that while wildtype PTEN induced apoptosis, the R234Q mutant did not.
Staal, F. J. T., van der Luijt, R. B., Baert, M. R. M., van Drunen, J., van Bakel, H., Peters, E., de Valk, I., van Amstel, H. K. P., Taphoorn, M. J. B., Jansen, G. H., van Veelen, C. W. M., Burgering, B., Staal, G. E. J. A novel germline mutation of PTEN associated with brain tumours of multiple lineages. Brit. J. Cancer 86: 1586-1591, 2002. [PubMed: 12085208] [Full Text: https://doi.org/10.1038/sj.bjc.6600206]