Molecular alterations in the neurofibromatosis Type 2 gene and its protein rarely occurring in meningothelial meningiomas

J. J. Evans, S. S. Jeun, J. H. Lee, J. A. Harwalkar, Y. Shoshan, John Kenneth Cowell, M. Golubic

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Object. The neurofibromatosis Type 2 (NF2) gene is the only tumor suppressor gene that has been clearly implicated in the development of benign meningiomas. Interestingly, previous data obtained by the authors indicate that reduced NF2 protein expression seldom occurs in meningothelial meningiomas, the most common histological type of meningioma. The goal of the current study was to explore further the hypothesis of NF2 gene-independent tumorigenesis of meningothelial meningiomas. Methods. The authors performed a mutational analysis of all 17 exons of the NF2 gene by using single-stranded conformational polymorphism (SSCP). In addition, expression levels of the NF2 protein and μ-calpain, a protease suggested to inactivate the NF2 protein, were determined immunoblotting analysis of 27 meningiomas (20 meningothelial and seven nonmeningothelial). Mutations of the NF2 gene were found in only one (5%) of 20 meningothelial meningiomas and three (43%) of seven nonmeningothelial tumors (Fisher's exact test, p = 0.042). The levels of NF2 protein were severely reduced in six (28.5%) of 21 meningothelial meningiomas, in contrast to six (86%) of seven nonmeningothelial meningiomas (Fisher's exact test, p = 0.023). Activation of μ-calpain did not correlate with the status of NF2 protein expression in the meningiomas analyzed, demonstrating that μ-calpain activation does not account for the loss of NF2 protein in meningiomas with apparently normal NF2 genes. Conclusions. These results clearly demonstrate that NF2 gene mutations and decreased NF2 protein expression rarely occur in meningothelial meningiomas compared with other histological types of meningiomas. The clinical behavior of meningothelial meningiomas, however, is similar to that of other benign meningiomas. It is likely, therefore, that the tumorigenesis of meningothelial meningiomas is the result of deleterious alterations of genes that have final phenotypical effects similar to inactivation of the NF2 gene.

Original languageEnglish (US)
Pages (from-to)111-117
Number of pages7
JournalJournal of neurosurgery
Volume94
Issue number1
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

Fingerprint

Neurofibromatosis 2 Genes
Neurofibromatosis 2
Meningioma
Neurofibromin 2
Proteins
Calpain
Carcinogenesis
Single-Stranded Conformational Polymorphism

Keywords

  • Calpain
  • Meningothelial meningioma
  • Neurofibromatosis
  • Tumorigenesis

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

Cite this

Molecular alterations in the neurofibromatosis Type 2 gene and its protein rarely occurring in meningothelial meningiomas. / Evans, J. J.; Jeun, S. S.; Lee, J. H.; Harwalkar, J. A.; Shoshan, Y.; Cowell, John Kenneth; Golubic, M.

In: Journal of neurosurgery, Vol. 94, No. 1, 01.01.2001, p. 111-117.

Research output: Contribution to journalArticle

Evans, J. J. ; Jeun, S. S. ; Lee, J. H. ; Harwalkar, J. A. ; Shoshan, Y. ; Cowell, John Kenneth ; Golubic, M. / Molecular alterations in the neurofibromatosis Type 2 gene and its protein rarely occurring in meningothelial meningiomas. In: Journal of neurosurgery. 2001 ; Vol. 94, No. 1. pp. 111-117.
@article{7ebbe1c015a740969713d93a176daccf,
title = "Molecular alterations in the neurofibromatosis Type 2 gene and its protein rarely occurring in meningothelial meningiomas",
abstract = "Object. The neurofibromatosis Type 2 (NF2) gene is the only tumor suppressor gene that has been clearly implicated in the development of benign meningiomas. Interestingly, previous data obtained by the authors indicate that reduced NF2 protein expression seldom occurs in meningothelial meningiomas, the most common histological type of meningioma. The goal of the current study was to explore further the hypothesis of NF2 gene-independent tumorigenesis of meningothelial meningiomas. Methods. The authors performed a mutational analysis of all 17 exons of the NF2 gene by using single-stranded conformational polymorphism (SSCP). In addition, expression levels of the NF2 protein and μ-calpain, a protease suggested to inactivate the NF2 protein, were determined immunoblotting analysis of 27 meningiomas (20 meningothelial and seven nonmeningothelial). Mutations of the NF2 gene were found in only one (5{\%}) of 20 meningothelial meningiomas and three (43{\%}) of seven nonmeningothelial tumors (Fisher's exact test, p = 0.042). The levels of NF2 protein were severely reduced in six (28.5{\%}) of 21 meningothelial meningiomas, in contrast to six (86{\%}) of seven nonmeningothelial meningiomas (Fisher's exact test, p = 0.023). Activation of μ-calpain did not correlate with the status of NF2 protein expression in the meningiomas analyzed, demonstrating that μ-calpain activation does not account for the loss of NF2 protein in meningiomas with apparently normal NF2 genes. Conclusions. These results clearly demonstrate that NF2 gene mutations and decreased NF2 protein expression rarely occur in meningothelial meningiomas compared with other histological types of meningiomas. The clinical behavior of meningothelial meningiomas, however, is similar to that of other benign meningiomas. It is likely, therefore, that the tumorigenesis of meningothelial meningiomas is the result of deleterious alterations of genes that have final phenotypical effects similar to inactivation of the NF2 gene.",
keywords = "Calpain, Meningothelial meningioma, Neurofibromatosis, Tumorigenesis",
author = "Evans, {J. J.} and Jeun, {S. S.} and Lee, {J. H.} and Harwalkar, {J. A.} and Y. Shoshan and Cowell, {John Kenneth} and M. Golubic",
year = "2001",
month = "1",
day = "1",
doi = "10.3171/jns.2001.94.1.0111",
language = "English (US)",
volume = "94",
pages = "111--117",
journal = "Journal of Neurosurgery",
issn = "0022-3085",
publisher = "American Association of Neurological Surgeons",
number = "1",

}

TY - JOUR

T1 - Molecular alterations in the neurofibromatosis Type 2 gene and its protein rarely occurring in meningothelial meningiomas

AU - Evans, J. J.

AU - Jeun, S. S.

AU - Lee, J. H.

AU - Harwalkar, J. A.

AU - Shoshan, Y.

AU - Cowell, John Kenneth

AU - Golubic, M.

PY - 2001/1/1

Y1 - 2001/1/1

N2 - Object. The neurofibromatosis Type 2 (NF2) gene is the only tumor suppressor gene that has been clearly implicated in the development of benign meningiomas. Interestingly, previous data obtained by the authors indicate that reduced NF2 protein expression seldom occurs in meningothelial meningiomas, the most common histological type of meningioma. The goal of the current study was to explore further the hypothesis of NF2 gene-independent tumorigenesis of meningothelial meningiomas. Methods. The authors performed a mutational analysis of all 17 exons of the NF2 gene by using single-stranded conformational polymorphism (SSCP). In addition, expression levels of the NF2 protein and μ-calpain, a protease suggested to inactivate the NF2 protein, were determined immunoblotting analysis of 27 meningiomas (20 meningothelial and seven nonmeningothelial). Mutations of the NF2 gene were found in only one (5%) of 20 meningothelial meningiomas and three (43%) of seven nonmeningothelial tumors (Fisher's exact test, p = 0.042). The levels of NF2 protein were severely reduced in six (28.5%) of 21 meningothelial meningiomas, in contrast to six (86%) of seven nonmeningothelial meningiomas (Fisher's exact test, p = 0.023). Activation of μ-calpain did not correlate with the status of NF2 protein expression in the meningiomas analyzed, demonstrating that μ-calpain activation does not account for the loss of NF2 protein in meningiomas with apparently normal NF2 genes. Conclusions. These results clearly demonstrate that NF2 gene mutations and decreased NF2 protein expression rarely occur in meningothelial meningiomas compared with other histological types of meningiomas. The clinical behavior of meningothelial meningiomas, however, is similar to that of other benign meningiomas. It is likely, therefore, that the tumorigenesis of meningothelial meningiomas is the result of deleterious alterations of genes that have final phenotypical effects similar to inactivation of the NF2 gene.

AB - Object. The neurofibromatosis Type 2 (NF2) gene is the only tumor suppressor gene that has been clearly implicated in the development of benign meningiomas. Interestingly, previous data obtained by the authors indicate that reduced NF2 protein expression seldom occurs in meningothelial meningiomas, the most common histological type of meningioma. The goal of the current study was to explore further the hypothesis of NF2 gene-independent tumorigenesis of meningothelial meningiomas. Methods. The authors performed a mutational analysis of all 17 exons of the NF2 gene by using single-stranded conformational polymorphism (SSCP). In addition, expression levels of the NF2 protein and μ-calpain, a protease suggested to inactivate the NF2 protein, were determined immunoblotting analysis of 27 meningiomas (20 meningothelial and seven nonmeningothelial). Mutations of the NF2 gene were found in only one (5%) of 20 meningothelial meningiomas and three (43%) of seven nonmeningothelial tumors (Fisher's exact test, p = 0.042). The levels of NF2 protein were severely reduced in six (28.5%) of 21 meningothelial meningiomas, in contrast to six (86%) of seven nonmeningothelial meningiomas (Fisher's exact test, p = 0.023). Activation of μ-calpain did not correlate with the status of NF2 protein expression in the meningiomas analyzed, demonstrating that μ-calpain activation does not account for the loss of NF2 protein in meningiomas with apparently normal NF2 genes. Conclusions. These results clearly demonstrate that NF2 gene mutations and decreased NF2 protein expression rarely occur in meningothelial meningiomas compared with other histological types of meningiomas. The clinical behavior of meningothelial meningiomas, however, is similar to that of other benign meningiomas. It is likely, therefore, that the tumorigenesis of meningothelial meningiomas is the result of deleterious alterations of genes that have final phenotypical effects similar to inactivation of the NF2 gene.

KW - Calpain

KW - Meningothelial meningioma

KW - Neurofibromatosis

KW - Tumorigenesis

UR - http://www.scopus.com/inward/record.url?scp=0034877128&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034877128&partnerID=8YFLogxK

U2 - 10.3171/jns.2001.94.1.0111

DO - 10.3171/jns.2001.94.1.0111

M3 - Article

VL - 94

SP - 111

EP - 117

JO - Journal of Neurosurgery

JF - Journal of Neurosurgery

SN - 0022-3085

IS - 1

ER -