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少突胶质细胞及少突胶质细胞瘤样肿瘤中的等位基因缺失:使用微卫星重复序列和聚合酶链反应的分析

Allelic losses in oligodendroglial and oligodendroglioma-like neoplasms: analysis using microsatellite repeats and polymerase chain reaction.

作者信息

Johnson Mahlon D, Vnencak-Jones Cindy L, Toms Steven A, Moots Paul M, Weil Robert

机构信息

Department of Pathology, Vanderbilt Medical School, Nashville, Tenn 37232, USA.

出版信息

Arch Pathol Lab Med. 2003 Dec;127(12):1573-9. doi: 10.5858/2003-127-1573-ALIOAO.

Abstract

CONTEXT

Oligodendroglial tumors are heterogenous neoplasms with histologic features shared with other central nervous system tumors, such as dysembryoplastic neuroepithelial tumors.

OBJECTIVE

We examined a series of tumors, identified as possessing oligodendroglial components at the time of intraoperative examination, to see if molecular subsets based on the oligodendroglial component could be recognized.

DESIGN

DNA was extracted from fresh brain tumor tissue and corresponding peripheral blood or normal tissues. Genotypes for multiple loci were determined by polymerase chain reaction amplification using fluorescent-labeled primers for markers on chromosomes 1p, 17p, and 19q.

RESULTS

Of the 12 oligodendrogliomas, 6 (60%) of 10 informative cases for 1p exhibited loss of heterozygosity (LOH). Six (50%) of 12 informative cases for 19q exhibited LOH. Each case also showed LOH at 1p. Three (25%) of 12 informative cases exhibited LOH at 17p for the dinucleotide repeat within the TP53 gene. In oligoastrocytomas, none of 4 informative cases showed LOH at 1p, 1 (25%) showed LOH at 19q, and 2 (50%) at 17p. One case also displayed microsatellite instability at 3 of 8 markers. In the 3 anaplastic oligodendrogliomas, 1 was not informative for 1p and none of the informative tumors exhibited LOH at 1p or 17p; 1 case (33%) exhibited LOH at 19q. Of the 14 informative anaplastic oligoastrocytomas, LOH was seen in 5 (36%) at both 1p and 19q and in 2 (14%) at 17p. Those with allelic loss at TP53 were astrocytoma predominant. No dysembryoplastic neuroepithelial tumors exhibited LOH at any marker on 1p, 17p, or 19q.

CONCLUSIONS

These findings suggest that routine screening for allelic losses, in samples intraoperatively determined to have an oligodendroglial component, will reveal prognostically or therapeutically relevant information in the majority of cases.

摘要

背景

少突胶质细胞瘤是一种异质性肿瘤,具有与其他中枢神经系统肿瘤(如胚胎发育不良性神经上皮肿瘤)共有的组织学特征。

目的

我们检查了一系列在术中检查时被确定具有少突胶质细胞成分的肿瘤,以确定是否能够识别基于少突胶质细胞成分的分子亚群。

设计

从新鲜脑肿瘤组织以及相应的外周血或正常组织中提取DNA。使用针对1号染色体、17号染色体短臂和19号染色体长臂上标记的荧光标记引物,通过聚合酶链反应扩增来确定多个位点的基因型。

结果

在12例少突胶质细胞瘤中,10例有信息可查的1号染色体短臂病例中有6例(60%)表现出杂合性缺失(LOH)。12例有信息可查的19号染色体长臂病例中有6例(50%)表现出杂合性缺失。每例病例在1号染色体短臂上也都表现出杂合性缺失。12例有信息可查的病例中有3例(25%)在TP53基因内的二核苷酸重复序列处表现出17号染色体短臂杂合性缺失。在少突星形细胞瘤中,4例有信息可查的病例在1号染色体短臂上均未表现出杂合性缺失,1例(25%)在19号染色体长臂上表现出杂合性缺失,2例(50%)在17号染色体短臂上表现出杂合性缺失。1例病例在8个标记中的3个处还表现出微卫星不稳定性。在3例间变性少突胶质细胞瘤中,1例在1号染色体短臂上无信息可查,有信息可查的肿瘤中无一例在1号染色体短臂或17号染色体短臂上表现出杂合性缺失;1例病例(33%)在19号染色体长臂上表现出杂合性缺失。在14例有信息可查的间变性少突星形细胞瘤中,5例(36%)在1号染色体短臂和19号染色体长臂上均出现杂合性缺失,2例(14%)在17号染色体短臂上出现杂合性缺失。TP53等位基因缺失的病例以星形细胞瘤为主。胚胎发育不良性神经上皮肿瘤在1号染色体短臂、17号染色体短臂或19号染色体长臂上的任何标记处均未表现出杂合性缺失。

结论

这些发现表明,对术中确定具有少突胶质细胞成分的样本进行等位基因缺失的常规筛查,将在大多数病例中揭示与预后或治疗相关的信息。

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