Rg. Weber et al., ANALYSIS OF GENOMIC ALTERATIONS IN BENIGN, ATYPICAL, AND ANAPLASTIC MENINGIOMAS - TOWARD A GENETIC MODEL OF MENINGIOMA PROGRESSION, Proceedings of the National Academy of Sciences of the United Statesof America, 94(26), 1997, pp. 14719-14724
Nineteen benign [World Health Organization (WHO) grade I; MI], 21 atyp
ical (WHO grade II; MH), and 19 anaplastic (WHO grade III; MIII) spora
dic meningiomas were screened for chromosomal imbalances by comparativ
e genomic hybridization (CGH), These data were supplemented by moleo u
lar genetic analyses of selected chromosomal regions and genes, With i
ncreasing malignancy grade, a marked accumulation of genomic aberratio
ns was observed; i.e., the numbers (mean +/- SEM) of total alterations
detected per tumor were 2.9 +/- 0.7 for MI, 9.2 +/- 1.2 for MII and 1
3.3 +/- 1.9 for MIII. The most frequent alteration detected in MI was
loss on 22q (58%), In MII, aberrations most commonly identified were l
osses on 1p (76%), 22q (71%), 14q (43%), 18q (43%), 10 (38%), and 6q (
33%), as well as gains on 20q (48%), 12q (43%), 15q (43%), 1q (33%), 9
q (33%), and 17q (33%). In MIII, most of these alterations were found
at similar frequencies, However, an increase in losses on 6q (53%), 10
(68%), and 14q (63%) was observed, In addition, 32% of MIII demonstra
ted loss on 9p, Homozygous deletions in the CDKV2A gene at 9p21 were f
ound in 4 of 16 MIII (25%), Highly amplified DNA sequences were mapped
to 12q13-q15 by CGH in 1 MII. Southern blot analysis of this tumor re
vealed amplification of CDK4 and MDM2. By CGH, DNA sequences from 17q
were found to be amplified in 1 MII and 8 Mm; involving 17q23 in all c
ases, Despite the high frequency of chromosomal aberrations in the MII
and Mm investigated, none of these tumors showed mutations in exons 5
-8 of the TP53 gene, On the basis of the most common aberrations ident
ified in the various malignancy grades, a model for the genomic altera
tions associated with meningioma progression is proposed.