Meningiomas: analysis of loss of heterozygosity on chromosome 10 in tumor progression and the delineation of four regions of chromosomal deletion in common with other cancers.
OBJECTIVE
Loss of heterozygosity (LOH) of alleles on chromosome 10 has been reported in many cancers, leading to the identification of tumor suppressor genes on this chromosome. Several reports implicate LOH of chromosome 10 alleles in meningioma progression, but the frequency and complexity of the loss have not been well characterized. Furthermore, the location and identity of the putative tumor suppressor genes on this chromosome that contribute to meningioma progression are unknown because the currently characterized tumor suppressor genes do not appear to be involved. Therefore, this study was undertaken to (a) assess the frequency and complexity of LOH in meningioma progression, (b) map the LOH patterns of individual meningiomas to define the smallest regions of shared chromosomal deletion, and (c) compare the identified regions with chromosome 10 deletions in other cancers, and thereby initiate the localization of the putative tumor suppressor genes.


METHODS
We examined 11 microsatellite dinucleotide repeat loci in 208 meningiomas of all grades using laser capture microdissection and fluorescence-based detection of PCR products.


RESULTS
For all markers examined, the incidence of LOH was much higher in all grades than that previously reported, with incidence and complexity of LOH increasing with tumor grade. LOH mapping identified four regions of chromosomal deletion: 10pter-D10S89, D10S109-D10S215, D10S187-D10S209, and D10S169-10qter. These deletions on chromosome 10 are shared with other cancer types.


CONCLUSIONS
These results delineate chromosomal locations of putative tumor suppressor genes on chromosome 10 that likely play an early role in meningioma tumorigenesis as well as tumor progression.
Mihaila
Dana
D
Hermelin Brain Tumor Center, Henry Ford Health Sciences Center, Detroit, Michigan 48202, USA.
Gutiérrez
Jorge A
JA
Rosenblum
Mark L
ML
Newsham
Irene F
IF
Bögler
Oliver
O
Rempel
Sandra A
SA
D001921:Brain / Q000473:pathology; D002872:Chromosome Deletion; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D018900:Dinucleotide Repeats; D018450:Disease Progression; D005787:Gene Frequency; D016147:Genes, Tumor Suppressor; D006801:Humans; D007834:Lasers; D019656:Loss of Heterozygosity; D008214:Lymphocytes / Q000473:pathology; D008577:Meningeal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008579:Meningioma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D018895:Microsatellite Repeats; D009369:Neoplasms / Q000235:genetics; D016133:Polymerase Chain Reaction
D004273:DNA, Neoplasm