Nervous system tumors: Meningioma

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Nervous system tumors: 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 (left); typical meningioma with Homer-Wright rosettes ((right)) - 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, ChordoŒd 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.

External links

OMIM 156100

Orphanet Meningioma

Bibliography

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Correlation between clinical and cytogenetical data in 180 meningiomas.

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On the pathology of meningiomas. A study of 412 cases.

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Genetic linkage of bilateral acoustic neurofibromatosis to a DNA marker on chromosome 22.

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Molecular genetic approach to human meningioma: loss of genes on chromosome 22.

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Molecular genetic analysis of chromosome 22 in 81 cases of meningioma.

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Classic, atypical, and anaplastic meningioma: three histopathological subtypes of clinical relevance.

Maier H, Ofner D, Hittmair A, Kitz K, Budka H.

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Telomeric association of chromosomes in human meningiomas.

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Abnormalities of chromosome 22 in human brain tumors determined by combined cytogenetic and molecular genetic approaches.

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Frequent NF2 gene transcript mutations in sporadic meningiomas and vestibular schwannomas.

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

Lindblom A, Ruttledge M, Collins VP, Nordenskjold M, Dumanski JP.

Int J Cancer 1994; 56: 354-357.

Cytogenetic, molecular genetic and pathological analyses in 126 meningiomas.

Lekanne Deprez RH, Riegman PH, van Drunen E, Warringa UL, Groen NA, Stefanko SZ, Koper JW, Avezaat CJ, Mulder PG, Zwarthoff EC.

J Neuropathol Exp Neurol 1995; 54: 224-235.

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.

Oncogene 1995; 10: 1521-1528.

Neuropathology and molecular genetics of neurofibromatosis 2 and related tumors.

Louis DN, Ramesh V, Gusella JF.

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Somatic mutations in the neurofibromatosis type 2 gene in sporadic meningiomas.

Papi L, De Vitis LR, Vitelli F, Ammannati F, Mennonna P, Montali E, Bigozzi U.

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Analysis of the neurofibromatosis 2 gene reveals molecular variants of meningioma.

Wellenreuther R, Kraus JA, Lenartz D, Menon AG, Schramm J, Louis DN Ramesh V, Gusella JF, Wiestler OD, von Deimling A.

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Contributor(s)

Written 07-2000 Anne Marie Capodano

Citation

This paper should be referenced as such :
Capodano AM . Nervous system tumors: Meningioma. Atlas Genet Cytogenet Oncol Haematol. July 2000 .
URL : http://AtlasGeneticsOncology.org/Tumors/MeningiomaID5014.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Thu Apr 17 14:14:38 2008

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Note	Macroscopic aspect of a parassagital meningioma - Anne Marie Capodano

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 (left); typical meningioma with Homer-Wright rosettes ((right)) - 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, ChordoŒd 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 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

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.

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