Hartmann Christian, Nümann Astrid, Mueller Wolf, Holtkamp Nikola, Simon Matthias, von Deimling Andreas
Department of Neuropathology, Charité, Campus Virchow Klinikum, Humboldt University, Augustenburgerplatz 1, D-13353 Berlin, Germany.
Int J Cancer. 2004 Mar 1;108(6):839-44. doi: 10.1002/ijc.11638.
Astrocytomas and glioblastomas are the most frequent primary brain tumors in adults. Mutations and altered expression of multiple genes have been found to contribute to the genesis of these tumors. However, many factors in the genesis of astrocytic gliomas are not resolved yet. The frequent losses on several chromosomes indicate the role of still unidentified tumor suppressor genes. Loss of heterozygosity (LOH) on 22q has been described in up to 30% of astrocytic tumors and may be associated with progression to anaplasia. In a first step, information from the nearly finished physical sequence of chromosome 22 were used to map LOH data from 22q deletion studies on different tumor entities to identify potential tumor suppressor gene candidate regions. Next, a series of 153 astrocytic gliomas was examined with 11 polymorphic markers spanning these regions. Forty-nine (32%) astrocytic gliomas exhibited LOH on 22q, 17 (35%) of which lost heterozygosity for all markers and 32 (65%) of which carried interstitial or partial deletions. Two regions were identified on the physical DNA sequence. The centromeric region spans 3 Mb and the telomeric region 2.7 Mb. The reduced size of these regions now allows direct analysis of all genes included. We already performed mutation analysis on 4 candidate genes from these regions (MYO18B, DJ1042K10.2, MKL1 and EP300), but did not find any mutations in astrocytic tumors.
星形细胞瘤和胶质母细胞瘤是成人中最常见的原发性脑肿瘤。已发现多个基因的突变和表达改变促成了这些肿瘤的发生。然而，星形细胞胶质瘤发生过程中的许多因素仍未得到解决。几条染色体上的频繁缺失表明仍未确定的肿瘤抑制基因的作用。在高达30%的星形细胞肿瘤中已描述了22号染色体长臂上的杂合性缺失（LOH），其可能与向间变的进展相关。第一步，利用来自22号染色体近乎完成的物理序列的信息，将来自不同肿瘤实体的22号染色体长臂缺失研究的LOH数据进行定位，以识别潜在的肿瘤抑制基因候选区域。接下来，用跨越这些区域的11个多态性标记对一系列153例星形细胞胶质瘤进行检测。49例（32%）星形细胞胶质瘤在22号染色体长臂上表现出LOH，其中17例（35%）对所有标记均失去杂合性，32例（65%）存在间质或部分缺失。在物理DNA序列上确定了两个区域。着丝粒区域跨度为3 Mb，端粒区域为2.7 Mb。这些区域缩小的大小现在允许对其中包含的所有基因进行直接分析。我们已经对来自这些区域的4个候选基因（MYO18B、DJ1042K10.2、MKL1和EP300）进行了突变分析，但在星形细胞肿瘤中未发现任何突变。
