Glioma Susceptibility 1

Alternative Names

  • GLM1
  • Glioma of Brain, Familial
  • GLM
  • Glioblastoma Multiforme
  • GBM
  • Astrocytoma
  • Oligodendroglioma
  • Ependymoma
  • Subependymoma
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WHO-ICD-10 version:2010

Neoplasms

Malignant neoplasms

OMIM Number

137800

Mode of Inheritance

Autosomal dominant; Somatic mutation

Gene Map Locus

2q34,17p13.1, 17q12

Description

Glioblastoma Multiforme (GLM) is an aggressive, malignant neoplasm of the brain, characterized by the presence of small areas of necrotizing tissue, surrounded by highly anaplastic cells. These tumors may arise from neural stem cells and appear to contain tumor stem cells. The tumors are seen to develop most commonly in the cerebral hemispheres, followed by the thalamus, hypothalamus, and the posterior fossa, but very rarely in the cerebellum. General symptoms include headache, lethargy, seizures, nausea, compression of surrounding brain structures, weakness, neuroendocrine abnormalities, and behavioral changes. The tumors tend to occur most commonly between the fifth and sixth decades of life and are equally common in men and women.

MRI and CAT are the most useful methods for detecting the tumors, although a biopsy is required to confirm the diagnosis. Supportive treatment makes use of anticonvulsants to manage the seizures, and corticosteroids to reduce the intracranial pressure. Palliative treatment, on the other hand, makes use of surgery, radiation therapy, and chemotherapy to prolong survival. Prognosis for the condition is very poor. The mean survival length is only eight to ten months after diagnosis. Prospects are slightly better for younger patients and in patients in whom the entire tumor could be surgically removed.

Gliomas have been noticed to occur frequently in association with other genetic disorders, such as Li-Fraumeni Syndrome 1, a cancer predisposition syndrome caused by mutation in the Tumor Protein p53 (TP53) gene on chromosome 17p13. Somatic mutation, disruption, or copy number variation of the following genes or loci may also contribute to the formation of glioma: ERBB (EGFR; Epidermal Growth Factor Receptor), ERBB2, LGI1, GAS41, GLI, DMBT1, IDH1, IDH2, BRAF, PARK2, RB1, PIK3CA, 10p15, 19q, and 17p13.3. In an interesting study, MGMT hypermethylation was found to be associated with long-term survival in affected individuals.

Molecular Genetics

Gliomas have been noticed to occur frequently in association with other genetic disorders, such as Li-Fraumeni Syndrome 1, a cancer predisposition syndrome caused by mutation in the Tumor Protein p53 (TP53) gene on chromosome 17p13. Somatic mutation, disruption, or copy number variation of the following genes or loci may also contribute to the formation of glioma: ERBB (EGFR; Epidermal Growth Factor Receptor), ERBB2, LGI1, GAS41, GLI, DMBT1, IDH1, IDH2, BRAF, PARK2, RB1, PIK3CA, 10p15, 19q, and 17p13.3. In an interesting study, MGMT hypermethylation was found to be associated with long-term survival in affected individuals.

Epidemiology in the Arab World

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Other Reports

Oman

George and Samarasinghe (2002) reported the histo-pathological features of gliosarcoma from a tissue obtained from a 66-year old male who presented with two months history of headache, vomiting and seizures. As CT scan of brain revealed a left tempro-parietal mass with mixed density and minimum enhancement, it was subtotaly excised. Macroscopically, this mass was light brown in color with firm consistency and, microscopically, it had a mixture of neoplastic, meshenchymal and glial elements which was diagnostic of gliosarcoma. These diagnostic features were glial appearance with astrocytic anaplasia, giant cells, and necrotic foci, with some pleomorphic cells being GFAP positive (glial fibrillary acid protein) with brisk mitotic activity and abnormal mitosis. Undifferentiated spindle cells in fascicles with some being positive for vimentin and GFAP were also seen. In addition to that, malignant osteoid and chondroid tissues were detected, with S100 positivity in the latter.

[George E, Samarasinghe D. Gliosarcoma - Pathology and review of literature. Oman Med J. 2002; 19(1):58-60.]

Palestine

In a highly inbred Arab family, Chemke et al. (1985) observed five cases of glioblastoma multiforme in two sibships. Curiously, all were male and, in all, the tumor was located on the right side of the brain. The ages of presentation ranged from 4 to 11 years. 'Astrocytoma type 3' was the histologic diagnosis. Chemke et al. (1985) indicated that in this family the tumor develops as the consequence of an autosomal recessive or an X-linked recessive mutation. In addition, the gene for cystic fibrosis segregates in this family and an undefined autosomal recessive malformation syndrome was detected.

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