Nervous system: Meningioma

Identity

ICD-Topo	C700-C701,C709 MENINGES (CEREBRAL,SPINAL)
ICD-Morpho	9530/0 Meningioma, NOS / Microcystic meningiom / Secretory meningioma / Lymphoplasmacyte-rich meningioma / Metaplastic meningioma
Atlas_Id	5014
Phylum	Central Nervous system::Meningioma

Classification

Note	Macroscopic aspect of a parassagital meningioma - Anne Marie Capodano.

Clinics and Pathology

Disease	Meningiomas are tumors arising from cells of the meningeal covering of the brain and spinal cord. These tumors are generally slow growing masses. Neurological signs and symptoms appear by compression of adjacent structures.
Etiology	Meningiomas are known to be induced by radiation with an average time interval to tumor appearence of 20-35 years. The majority of patients with radio-induced meningiomas have received irradiation for tinea capitis or for primary brain tumor.
Epidemiology	Meningiomas account for 15-25% of primary intracranial and intraspinal neoplasms, with an annual incidence of approximatively 6 per 100.000 individuals. Meningiomas are often multiple in patients with neurofibromatosis type 2 (NF2). Sporadic meningiomas may also be multiple. Meningiomas are most common during the sixth and seventh decade of life, but can occur in both childrens and in the elderly. There is a marked high frequency in females.
Clinics	The vast majority of meningiomas arise within the intracranial, orbital, and intravertebral cavities.
	Histological features of a fibroblastic meningioma - Anne Marie Capodano.
Pathology	According to the World Health Classification (WHO 1993), the tumors are defined as Meningiothelial meningioma, Fibroblastic meningioma, Transitional meningioma, Psamommatous meningioma, Angiomatous meningioma, Chordoïd meningioma., and are classified according to increased degrees of anaplasia in grades I, II and III. 90% of meningiomas are slowly growing benign tumors that histologically correspond to grade I according WHO classification. 6-8% of meningiomas are designated as atypical meningiomas : WHO grade II. These tumors show a tendancy for local recurrence even after complete resection. 2-3% of meningiomas exibit histological signs of malignancy : these tumors are classified as anaplastic malignant meningiomas of WHO grade III. They have a high risk for local recurrence and metastasis.
Treatment	The treatment consists of total surgical resection of tumor.
Prognosis	The major evolution is recurrence. The tumor grade provides the most useful predictor of recurrence. Benign meningiomas have a recurrence rate of about 7-20%. Atypical meningiomas recur in 29-38% of cases, and anaplastic meningiomas in 50-78% of cases. So, proliferation indices have been used to predict recurrence and survival.

Cytogenetics

Cytogenetics Morphological	Meningiomas were among the first solid tumors recognized as having cytogenetic alterations. The most consistent change reported in benign meningiomas is partial (del(22)(q12)) or total deletion of chromosome 22. Loss of chromosome 22 more often occurs in meningiomas grade I. Other karyotypic abnormalities, associated or not with monosomy 22, are seen in grade II (atypical meningiomas), and grade III (anaplastic meningiomas); The most frequent abnormalities changes are deletion of the short arm of chromosome 1, partial or complete loss of chromosome 10, and loss of chromosome 14. Unstable chromosome alterations including rings, dicentrics and telomeric associations, have been observed. A statistical correlation between fibroblastic type and some chromosome abnormalities (monosomy 22 and telomeric associations), was reported. Studies support a postulated role of chromosome 22 as the primary event in the developpement of the majority of the meningiomas.
	Top: del(22q) (G-banding) - Courtesy G. Reza Hafez, Eric B. Johnson, Sara Morrison-Delap Cytogenetics at the Waisman Center; bottom: partial karyotype of a fibroblatic meningioma cell; there was hypoploidy (39,XX), a monosommy 22 (arrow), and tas (arrowheads) - Courtesy Anne Marie Capodano.

Genes involved and Proteins

Note

Allelic losses: Molecular genetic findings using polymorphic DNA markers, confirmed that half of meningiomas have allelic loss of band q12 on chromosome 22. Atypical and anaplastic meningiomas often show allelic losses of chromosomal arms 1p, 9q, 10q, 14q, and 17p. LOH of chromosome 14 was the most frequent abnormality in atypical meningiomas : for this reason it is considered to be a step of malignant progression.

Gene Name	NF2
Location	22q12
Dna / Rna	Tumor suppressor gene
Protein	Called merlin or schwannomin
Germinal mutation	In neurofibromatosis type 2 patients
Somatic mutation	Mutations in the NF2 gene are detected in aproximatively in 60% of sporadic meningiomas. The majority of mutations are small insertions, deletions or non-sens mutations that affect splice sites. The common effect of such mutations is a truncated merlin protein. The frequency of NF2 gene mutations varies according to the meningiomas types. Few mutations of NF2 gene were observed in meningothelial meningiomas : only 25% of cases. 70-80% of fibroblastic and transitional meningiomas carry NF2 gene mutations. Mutations and allelic loss events are also found in other tumors (schwannomas) and in neurofibromatosis type 2 tumours.

Note

LOH studies on chromosome 22 have also detected losses of genetic material outside the NF2 region. NF2 is likely to be the major tumor suppressor gene of meningiomas, but other genes localized in other loci on chromosome 22 are probably involved. Another candidate gene on chromosome 22 is MN1 wich has been implicated in a case of translocation in a meningioma. PTEN mutations, a gene localized in 10q23, were described in anaplastic meningiomas. Rare mutations were reported on the CDKN2A gene.

Bibliography

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Cloning and characterization of MN1, a gene from chromosome 22q11, which is disrupted by a balanced translocation in a meningioma.

Lekanne Deprez RH, Riegman PH, Groen NA, Warringa UL, van Biezen NA, Molijn AC, Bootsma D, de Jong PJ, Menon AG, Kley NA

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Chromosomal deletions in anaplastic meningiomas suggest multiple regions outside chromosome 22 as important in tumor progression.

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Telomeric association of chromosomes in human meningiomas.

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Citation

This paper should be referenced as such :

Capodano, AM

Nervous system tumors: Meningioma

Atlas Genet Cytogenet Oncol Haematol. 2000;4(3):149-152.

Free journal version : [ pdf ]   [ DOI ]

On line version : http://AtlasGeneticsOncology.org/Tumors/MeningiomaID5014.html

Other genes implicated (Data extracted from papers in the Atlas) [ 25 ]

Genes	AKT1S1	AQP4	BMP4	CAV1	CD248	CKS2	CTSL	DIO2	EIF3C	EIF4E
	ENO1	EPB41L3	MEN1	MKI67	NAT2	NF2	NRCAM	EP300	PTCH2	PTPRJ
	RAC2	RAC3	RACGAP1	TPX2	WNK2

External links

arrayMap	Topo ( C70) arrayMap ((UZH-SIB Zurich)   [auto + random 100 samples .. if exist ]   [tabulated segments]
Disease database	Nervous system: Meningioma

REVIEW articles	automatic search in PubMed
Last year articles	automatic search in PubMed

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