Molecular genetic approach to human meningioma: loss of genes on chromosome 22.
Molecular genetic approach to human meningioma: loss of genes on chromosome 22.
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人类脑膜瘤的分子遗传学方法：22 号染色体上的基因丢失。
DOI：
10.1073/pnas.84.15.5419
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发表时间：
1987
影响因子：
11.1
通讯作者：
Martuza,RL
中科院分区：
文献类型：
--
作者：
Seizinger,BR;delaMonte,S;Atkins,L;Gusella,JF;Martuza,RL
采用多态性 DNA 标记的分子遗传学方法已被用来研究染色体畸变在脑膜瘤中的作用，脑膜瘤是人类神经系统最常见的肿瘤之一。将肿瘤 DNA 中的 DNA 标记检测到的等位基因与正常组织中的 DNA 进行比较，揭示了原发性手术标本中存在的染色体改变。与培养脑膜瘤的细胞遗传学研究一致，检测到的最常见的改变是 22 号染色体上杂合性的丧失。51 名患者中的 40 名患者至少有一个 22 号染色体 DNA 标记为杂合性。 40 名固有杂合患者中有 17 名 (43%) 在其脑膜瘤肿瘤组织中表现出相应标记的半合性。其他几个常染色体上的标记也以显着较低的频率检测到杂合性丢失。鉴于双侧听神经纤维瘤病中听神经瘤和脑膜瘤之间的显着关联，以及听神经瘤在 22 号染色体上表现出特定基因缺失的发现，我们提出涉及 22 号染色体的共同机制在两种肿瘤类型的发展中发挥着作用。揭示脑膜瘤中部分缺失的精细结构图谱可能提供克隆和表征对人类神经系统肿瘤发生和可能的其他临床相关肿瘤的肿瘤发生至关重要的基因的方法。
A molecular genetic approach employing polymorphic DNA markers has been used to investigate the role of chromosomal aberrations in meningioma, one of the most common tumors of the human nervous system. Comparison of the alleles detected by DNA markers in tumor DNA versus DNA from normal tissue revealed chromosomal alterations present in primary surgical specimens. In agreement with cytogenetic studies of cultured meningiomas, the most frequent alteration detected was loss of heterozygosity on chromosome 22. Forty of 51 patients were constitutionally heterozygous for at least one chromosome 22 DNA marker. Seventeen of the 40 constitutionally heterozygotic patients (43%) displayed hemizygosity for the corresponding marker in their meningioma tumor tissues. Loss of heterozygosity was also detected at a significantly lower frequency for markers on several other autosomes. In view of the striking association between acoustic neuroma and meningioma in bilateral acoustic neurofibromatosis and the discovery that acoustic neuromas display specific loss of genes on chromosome 22, we propose that a common mechanism involving chromosome 22 is operative in the development of both tumor types. Fine-structure mapping to reveal partial deletions in meningiomas may provide the means to clone and characterize a gene (or genes) of importance for tumorigenesis in this and possibly other clinically associated tumors of the human nervous system.