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Molecular
pathogenesis of meningiomas
Arie
Perry, David H. Gutmann, Guido Reifenberger
Division
of Neuropathology, School of Medicine, St. Louis [A.P.];
Department of Neurology, Washington University School of Medicine,
St. Louis, MOUSA [D.H.G.]; Department of Neuropathology,
Henrich-Heine University, Düsseldorf,
Germany [G.R.].
Meningiomas
are common central nervous system tumors that originate from the
meningeal coverings of the brain and the spinal cord.
Most meningiomas are slowly growing benign tumors that
histologically correspond to World Health Organization (WHO) grade
I.
However, certain rare histological variants (clear cell, chordoid,
papillary, and rhabdoid), as well as atypical (WHO grade II) and
anaplastic (WHO grade III) meningiomas show a more aggressive
biological behavior and are clinically associated with a high risk
of local recurrence and a less favorable prognosis.
This review summarizes the most important features of meningioma
pathology and provides an up-to-date overview about the molecular
mechanisms involved in meningioma initiation and
progression.
Current data indicate that meningioma initiation is closely linked
to the inactivation of one or more members of the highly conserved
protein 4.1 superfamily, including the neurofibromatosis type 2
gene product merlin/schwannomin, protein 4.IB (DAL-1) and protein
4.1R.
The genetic alterations in atypical meningiomas are complex and
involve losses on 1p, 6q, 10, 14q and 18q, as well as gains on
multiple chromosomes.
The relevant genes are still unknown.
Anaplastic meningiomas show even more complex genetic alterations,
including frequent alteration of the CDKN2A,
p14ARF,
and CDKN2B
tumor
suppressor genes at 9p21, as well as gene amplification on
17q23.
A better understanding of the molecular mechanisms involved in
meningioma pathogenesis may not only lead to the identification of
novel diagnostic and prognostic marker but will also facilitate
the development of new pathogenesis-based therapeutic strategies.
Keywords:
meningioma,
molecular genetics, pathology, protein 4.1 tumor, suppressor gene
Copyright
©
2004 Kluwer Academic Publishers. All
rights reserved
Source:
http://ipsapp007.kluweronline.com/IPS/content/ext/x/J/5042/I/125/A/5/abstract.htm
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