Deletions on chromosome 22 in sporadic meningioma.
Meningiomas are the second most common group of primary central nervous system tumors in humans. Cytogenetic and molecular studies imply that genes involved in the primary development of meningioma reside on chromosome 22. The recently characterized neurofibromatosis type 2 gene (NF2) has been shown to be mutated in two cases of sporadic meningioma, suggesting that this is the chromosome 22 gene which is involved in tumorigenesis. We have investigated a series of 170 meningiomas by deletion mapping analysis with 43 markers from chromosome 22 to ascertain if NF2 is the only gene on this autosome that is inactivated. Half of the tumors showed results consistent with monosomy for chromosome 22, whereas 13 cases showed terminal deletions of 22q, including the NF2 region. Homozygous (complete) deletions were detected in tumors from two patients. In one of them complete loss was found at the NF2 locus and cosmid contigs from the region were used to determine the extent of the deletions. The second tumor showed homozygous loss of two large genomic regions outside the NF2 region. These aberrations were confined to only one part of this large tumor, suggesting that they may be involved in the later stages of meningioma development. An additional four tumors had interstitial deletions on chromosome 22, in three of them without overlap with NF2. Our results show that NF2 is completely inactivated in sporadic meningioma but do not rule out the possibility that additional chromosome 22 loci are important in tumorigenesis.
Ruttledge
M H
MH
Ludwig Institute for Cancer Research, Karolinska Hospital, Stockholm, Sweden.
Xie
Y G
YG
Han
F Y
FY
Peyrard
M
M
Collins
V P
VP
Nordenskjöld
M
M
Dumanski
J P
JP
D001483:Base Sequence; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22; D004247:DNA / Q000097:blood / Q000302:isolation & purification; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000097:blood / Q000302:isolation & purification; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D008579:Meningioma / Q000145:classification / Q000235:genetics* / Q000473:pathology; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods; D015183:Restriction Mapping
D017931:DNA Primers; D004273:DNA, Neoplasm; D005819:Genetic Markers; D004247:DNA