端粒和着丝粒不稳定性在脑膜瘤患者染色体畸变进展中的作用。

A role for telomeric and centromeric instability in the progression of chromosome aberrations in meningioma patients.

作者信息

Sawyer J R, Husain M, Pravdenkova S, Krisht A, Al-Mefty O

机构信息

Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.

出版信息

Cancer. 2000 Jan 15;88(2):440-53.

PMID:10640979

Abstract

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.

摘要

背景

脑膜瘤的主要染色体畸变是22号染色体单体或缺失。常见的继发性畸变包括1p、14q和10q染色体的缺失或丢失，以及不稳定的染色体畸变，如环状染色体、双着丝粒染色体和端粒联合。尽管通过细胞遗传学和分子技术对数百个肿瘤进行了分析，但脑膜瘤染色体畸变进展所涉及的机制仍知之甚少。

方法

采用短期原位技术成功培养了67例脑膜瘤，并结合溴化乙锭高分辨率G显带技术进行收获。

结果

26例肿瘤（39%）显示核型正常，而41例肿瘤（61%）显示克隆性染色体畸变。最常观察到的畸变是22号染色体缺失或涉及22q12的结构畸变，30例肿瘤（45%）出现这种情况。第二常见的畸变是涉及1q10着丝粒断点的全臂易位，导致12例肿瘤（18%）中整个1p染色体丢失。2例肿瘤显示一种新的、反复出现的、不平衡的全臂易位der(1;2)(q10;q10)。第三种畸变，端粒联合，在16例肿瘤（24%）中观察到，11例肿瘤中短暂出现，5例肿瘤中克隆性复发。7例肿瘤（10%）中发现双着丝粒22号染色体，2例肿瘤中发现22q物质逐渐丢失。