title: Analysis of human meningiomas for aberrations of the MADH2, MADH4, APM-1 and DCC tumor suppressor genes on the long arm of chromosome 18.
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-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.
authors: Department of Pathology, Division of Molecular Histopathology, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors: R
authors: R
authors: Büschges
authors: J
authors: J
authors: Boström
authors: M
authors: M
authors: Wolter
authors: B
authors: B
authors: Blaschke
authors: R G
authors: RG
authors: Weber
authors: P
authors: P
authors: Lichter
authors: V P
authors: VP
authors: Collins
authors: G
authors: G
authors: Reifenberger
mesh_terms: D052242:Adiponectin; D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D017398:Alternative Splicing; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002648:Child; D002869:Chromosome Aberrations; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D000075389:DCC Receptor; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D019656:Loss of Heterozygosity; D008297:Male; D008578:Meninges / Q000378:metabolism; D008579:Meningioma / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D009693:Nucleic Acid Hybridization; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051899:Smad2 Protein; D051901:Smad4 Protein; D015534:Trans-Activators / Q000235:genetics*; D025521:Tumor Suppressor Proteins
chemical_list: D052242:Adiponectin; D015815:Cell Adhesion Molecules; D000075389:DCC Receptor; C501909:DCC protein, human; D004268:DNA-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C497782:SMAD2 protein, human; C497796:SMAD4 protein, human; D051899:Smad2 Protein; D051901:Smad4 Protein; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins