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 aberratio ns including rings, dicentrics, and telomeric associations. Despite the ana lysis of several hundred tumors by cytogenetic and molecular techniques, th e mechanisms involved in the progression of chromosome aberrations in menin gioma remain poorly understood. METHODS. Sixty-seven meningiomas were cultured successfully using a short t erm in situ technique and harvested incorporating a high resolution G-bandi ng technique with ethidium bromide. RESULTS. Twenty-six tumors (39%) showed normal karyotypes, whereas 41 tumor s (61%) showed clonal chromosome aberrations. The most frequently observed aberration was the loss of chromosome 22 or structural aberrations involvin g 22q12, which occurred in 30 tumors (45%). The second most common aberrati ons were whole arm translocations involving the centromeric breakpoint at 1 q10, resulting in the loss of the entire 1p chromosome in 12 tumors (18%). Two tumors showed a new, recurring, unbalanced, whole arm translocation der (12)(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 mening ioma is mediated in some respects by both telomeric and centromeric instabi lity. 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 Ip detected by mo lecular analysis. (C) 2000 American Cancer Society.