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Molecular genetic analysis of ependymal tumors. NF2 mutations and chromosome 22q
loss occur preferentially in intramedullary spinal ependymomas
Ebert C, von Haken M,
Meyer-Puttlitz B, Wiestler OD, Reifenberger G, Pietsch T, von Deimling A
Department of
Neuropathology, University of Bonn Medical Center, Bonn Charite, Humboldt
University, Berlin, Germany.
Ependymal tumors are heterogeneous with regard to morphology, localization, age
at first clinical manifestation, and prognosis.
Several molecular alterations have been reported in these tumors, including
allelic losses on chromosomes 10, 17, and 22 and mutations in the NF2
gene.
However, in contrast to astrocytic gliomas, no consistent molecular alterations
have been associated with distinct types of ependymal tumors.
To evaluate whether morphological subsets of ependymomas are characterized by
specific genetic lesions, we analyzed a series of 62 ependymal tumors, including
myxopapillary ependymomas, subependymomas, ependymomas, and anaplastic
ependymomas, for allelic losses on chromosome arms 10q and 22q and mutations in
the PTEN and NF2 genes.
Allelic losses on 10q and 22q were detected in 5 of 56 and 12 of 54 tumors,
respectively.
Six ependymomas carried somatic NF2 mutations, whereas no mutations were
detected in the PTEN gene.
All six of the NF2 mutations occurred in ependymomas of WHO grade II and were
exclusively observed in tumors with a spinal localization (P = 0.0063).
These findings suggest that a considerable fraction of spinal ependymomas are
associated with molecular events involving chromosome 22 and that mutations in
the NF2 gene may be of primary importance for their genesis.
Furthermore, our data suggest that the more favorable clinical course of spinal
ependymomas may relate to a distinct pattern of genetic alterations different
from that of intracerebral ependymomas.
PMID: 10433955 [PubMed - indexed for MEDLINE]
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