Analysis of human meningiomas for aberrations of the MADH2, MADH4, APM-1 and DCC tumor suppressor genes on the long arm of chromosome 18 †
Rainer Büschges
Department of Pathology, Division of Molecular Histopathology, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom
Search for more papers by this authorJan Boström
Department of Neurosurgery, University of Bonn Medical Center, Bonn, Germany
Search for more papers by this authorMarietta Wolter
Department of Neuropathology, Heinrich-Heine-University, Düsseldorf, Germany
Search for more papers by this authorBritta Blaschke
Department of Neuropathology, Heinrich-Heine-University, Düsseldorf, Germany
Search for more papers by this authorRuthild G. Weber
Institute of Human Genetics, Ruprecht-Karls-University, Heidelberg, Germany
Search for more papers by this authorPeter Lichter
Abteilung Organisation komplexer Genome, Deutsches Krebsforschungszentrum, Heidelberg, Germany
Search for more papers by this authorV. Peter Collins
Department of Pathology, Division of Molecular Histopathology, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom
Search for more papers by this authorCorresponding Author
Guido Reifenberger
Department of Neuropathology, Heinrich-Heine-University, Düsseldorf, Germany
Fax: +49-211-811-7804
Department of Neuropathology, Heinrich-Heine-University, Moorenstrasse 5, D-40225 Düsseldorf, GermanySearch for more papers by this authorRainer Büschges
Department of Pathology, Division of Molecular Histopathology, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom
Search for more papers by this authorJan Boström
Department of Neurosurgery, University of Bonn Medical Center, Bonn, Germany
Search for more papers by this authorMarietta Wolter
Department of Neuropathology, Heinrich-Heine-University, Düsseldorf, Germany
Search for more papers by this authorBritta Blaschke
Department of Neuropathology, Heinrich-Heine-University, Düsseldorf, Germany
Search for more papers by this authorRuthild G. Weber
Institute of Human Genetics, Ruprecht-Karls-University, Heidelberg, Germany
Search for more papers by this authorPeter Lichter
Abteilung Organisation komplexer Genome, Deutsches Krebsforschungszentrum, Heidelberg, Germany
Search for more papers by this authorV. Peter Collins
Department of Pathology, Division of Molecular Histopathology, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom
Search for more papers by this authorCorresponding Author
Guido Reifenberger
Department of Neuropathology, Heinrich-Heine-University, Düsseldorf, Germany
Fax: +49-211-811-7804
Department of Neuropathology, Heinrich-Heine-University, Moorenstrasse 5, D-40225 Düsseldorf, GermanySearch for more papers by this authorThe first three authors contributed equally to this article.
Abstract
We have previously reported that losses of genomic material from the long arm of chromosome 18 are frequent in atypical and anaplastic meningiomas but rare in benign meningiomas. In the present study, we have investigated a series of 37 meningiomas for mutation and expression of 4 tumor suppressor genes (MADH2, MADH4, APM-1 and DCC) located at 18q21. Comparative genomic hybridization or loss of heterozygosity analysis showed losses on chromosome 18 that included sequences from 18q21 in 15 of 37 tumors. Mutation analysis of APM-1revealed a missense mutation (c. 1819G>A: G607S) in 1 atypical meningioma. None of the tumors showed mutations of MADH2 and MADH4 or loss of detectable transcripts from MADH2, MADH4, APM-1and DCC. In contrast to human brain tissue, normal leptomeninges and meningiomas showed preferential expression of a DCC splice variant lacking 60 base pairs from exon 17. Taken together, our data do not support a significant role for MADH2, MADH4, APM-1 and DCC alterations in the pathogenesis of meningiomas. The targeted gene that is inactivated in most meningiomas with 18q losses remains to be identified. © 2001 Wiley-Liss, Inc.
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