Molecular analysis of deletions of the short arm of chromosome 9 in human gliomas.
Molecular analysis of deletions of the short arm of chromosome 9 in human gliomas.
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发表时间：
1992-05
期刊：
影响因子：
11.2
通讯作者：
O. Olopade;Robert B. Jenkins;D. Ransom;Kathleen Malik;H. Pomykala;T. Nobori;Janet M. Cowan;J. Rowley;M. Diaz
中科院分区：
文献类型：
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作者：
O. Olopade;Robert B. Jenkins;D. Ransom;Kathleen Malik;H. Pomykala;T. Nobori;Janet M. Cowan;J. Rowley;M. Diaz
以前的研究表明，涉及9号染色体短臂的结构异常经常与胶质瘤有关。α-、β-和ω-干扰素（分别为IFNA、IFNB 1和IFNW）和甲硫腺苷磷酸化酶（MTAP）基因已定位于9号染色体的短臂，带p22。在许多白血病和神经胶质瘤衍生的细胞系中已经报道了这些基因的纯合缺失。在这份报告中，我们提出了一个详细的分析，部分和完全纯合或半合子缺失的DNA序列的9 p在人类细胞系和原发性肿瘤样本的神经胶质瘤患者。15个神经胶质瘤来源的细胞系中有10个（67%）具有IFN基因的半合子或纯合缺失或这些基因周围的序列重排，而35个原发性神经胶质瘤肿瘤样品中有13个（37%）具有IFN基因的半合子（8个肿瘤）或纯合（5个肿瘤）缺失。这些缺失的重叠的最短区域映射在IFN基因簇的着丝粒末端和MTAP基因之间的间隔中。在检查的细胞系和原发性肿瘤中，这些大体基因组改变仅与高级别或复发性胶质瘤相关。我们的观察结果证实，9 p上的DNA序列的丢失，特别是IFN基因，发生在一个显着的频率在胶质瘤，并可能代表这些肿瘤的进展中的一个重要步骤。这些结果与肿瘤发生模型一致，其中癌症的发展或进展涉及通常用于抑制肿瘤发生的一个或几个基因的丢失或失活。一个这样的基因可能位于9 p上;该基因可能与IFN基因紧密连锁。然而，当发生IFN基因的丢失时，可能在这些肿瘤的进展中发挥额外的作用。
Previous studies have suggested that structural abnormalities involving the short arm of chromosome 9 are frequently associated with gliomas. The alpha-, beta-, and omega-interferon (IFNA, IFNB1, and IFNW, respectively) and the methylthioadenosine phosphorylase (MTAP) genes have been mapped to the short arm of chromosome 9, band p22. Homozygous deletions of these genes have been reported in many leukemia- and glioma-derived cell lines. In this report, we present a detailed analysis of partial and complete homozygous or hemizygous deletions of DNA sequences on 9p in human cell lines and primary tumor samples of glioma patients. Ten of 15 (67%) glioma-derived cell lines had hemizygous or homozygous deletion of IFN genes or rearrangement of sequences around these genes, while 13 of 35 (37%) primary glioma tumor samples had hemizygous (8 tumors) or homozygous (5 tumors) deletion of the IFN genes. The shortest region of overlap of these deletions maps in the interval between the centromeric end of the IFN gene cluster and the MTAP gene. In the cell lines and primary tumors examined, these gross genomic alterations were seen only in association with high grade or recurrent gliomas. Our observations confirm that loss of DNA sequences on 9p, particularly the IFN genes, occurs at a significant frequency in gliomas, and may represent an important step in the progression of these tumors. These results are consistent with a model of tumorigenesis in which the development or progression of cancer involves the loss or inactivation of a gene or several genes that normally act to suppress tumorigenesis. One such gene may be located on 9p; this gene may be closely linked to the IFN genes. Nevertheless, loss of the IFN genes, when it occurs, may play an additional role in the progression of these tumors.