A role for telomeric and centromeric instability in the progression of chromosome aberrations in meningioma patients.
BACKGROUND
The primary chromosome aberration in meningiomas is monosomy or deletion of chromosome 22. Common secondary aberrations include losses or deletions of chromosomes 1p, 14q, and 10q and unstable chromosome aberrations including rings, dicentrics, and telomeric associations. Despite the analysis of several hundred tumors by cytogenetic and molecular techniques, the mechanisms involved in the progression of chromosome aberrations in meningioma remain poorly understood.


METHODS
Sixty-seven meningiomas were cultured successfully using a short term in situ technique and harvested incorporating a high resolution G-banding technique with ethidium bromide.


RESULTS
Twenty-six tumors (39%) showed normal karyotypes, whereas 41 tumors (61%) showed clonal chromosome aberrations. The most frequently observed aberration was the loss of chromosome 22 or structural aberrations involving 22q12, which occurred in 30 tumors (45%). The second most common aberrations were whole arm translocations involving the centromeric breakpoint at 1q10, resulting in the loss of the entire 1p chromosome in 12 tumors (18%). Two tumors showed a new, recurring, unbalanced, whole arm translocation der(1;2)(q10;q10). A third aberration, telomeric associations, were observed in 16 tumors (24%), occurring transiently in 11 tumors and recurring clonally in 5 tumors. Dicentric chromosome 22 was found in 7 tumors (10%), with the progressive loss of chromosome 22q material being found in 2 tumors.


CONCLUSIONS
The chromosome instability demonstrated in the current series of tumors suggests that the progression of chromosome aberrations in meningioma is mediated in some respects by both telomeric and centromeric instability. These two types of instability may be early events in the progression of chromosome aberrations in meningioma and each can account for at least some of the loss of heterozygosity of chromosomes 22q and 1p detected by molecular analysis.
Sawyer
J R
JR
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Husain
M
M
Pravdenkova
S
S
Krisht
A
A
Al-Mefty
O
O
D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002503:Centromere / Q000235:genetics*; D002869:Chromosome Aberrations / Q000235:genetics*; D019457:Chromosome Breakage; D002881:Chromosomes, Human, Pair 12; D002892:Chromosomes, Human, Pair 22; D005260:Female; D006801:Humans; D007621:Karyotyping; D008297:Male; D008579:Meningioma / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D016615:Telomere / Q000235:genetics*