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Analysis of human meningiomas for aberrations of the MADH2 , MADH4 , APM‐1 and DCC tumor suppressor genes on the long arm of chromosome 18
Author(s) -
Büschges Rainer,
Boström Jan,
Wolter Marietta,
Blaschke Britta,
Weber Ruthild G.,
Lichter Peter,
Collins V. Peter,
Reifenberger Guido
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.1219
Subject(s) - loss of heterozygosity , exon , missense mutation , biology , meningioma , chromosome 22 , mutation , cancer research , chromosome , genetics , gene , tumor suppressor gene , microbiology and biotechnology , pathology , carcinogenesis , allele , medicine
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‐1 revealed 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‐1 and 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.