Clonal genomic alterations in glioma malignancy stages.
Clonal genomic alterations in glioma malignancy stages.
复制标题
DOI：
--
复制
发表时间：
1988-10
期刊：
影响因子：
11.2
通讯作者：
C. James;E. Carlbom;J. Dumanski;Marc F. Hansen;Magnus Nordenskjöld;V. Collins;W. Cavenee
中科院分区：
文献类型：
--
作者：
C. James;E. Carlbom;J. Dumanski;Marc F. Hansen;Magnus Nordenskjöld;V. Collins;W. Cavenee
由限制性片段长度等位基因定义的染色体上的体质基因型和肿瘤基因型的比较已被证明有助于确定易患癌症的隐性突变的基因组位置和组织特异性（Hansen， M.F, and Cavenee， W.K.癌症研究，47:5518-5527,1987）。在这里，我们将这种方法应用于53例不同组织学恶性分级的不相关神经胶质肿瘤患者。组织学上被分类为胶质母细胞瘤的29个肿瘤中，有28个观察到10号染色体上基因座的结构杂合性缺失，而在22个恶性程度较低的胶质瘤中，没有观察到类似的缺失。对其他染色体上限制性片段长度等位基因的检查显示，13、17或22号染色体上的序列丢失以非随机频率发生，并且在成人胶质瘤的每个恶性级别中至少有一个实例。观察到结构杂合性缺失的肿瘤由一种或多种胶质细胞亚型组成，表现为星形细胞、少突胶质细胞和/或室管膜分化。这些结果表明，10号染色体序列的缺失与胶质瘤最恶性的组织学阶段密切相关，胶质母细胞瘤是早期前体的克隆扩增而产生的。此外，他们认为胶质母细胞瘤是各种细胞亚型胶质肿瘤的共同表型和恶性终点，并通过共同的分子途径达到。这种方法涉及识别恶性肿瘤阶段特异性体细胞杂合性损失，提供了肿瘤进展的基因型分析，而不是表型分析。
Comparison of constitutional and tumor genotypes at chromosomal loci defined by restriction fragment length alleles has proven useful in determining the genomic position and tissue specificity of recessive mutations that predispose to cancer (Hansen, M.F., and Cavenee, W.K. Cancer Res., 47:5518-5527, 1987). Here we have applied this approach to 53 unrelated patients with glial tumors of varying histological malignancy grade. Loss of constitutional heterozygosity for loci on chromosome 10 was observed in 28 of 29 tumors histologically classified as glioblastoma (malignancy grade IV) whereas no similar losses were observed in any of 22 gliomas of lower malignancy grade. Examination of restriction fragment length alleles on other chromosomes revealed that loss of sequences on chromosomes 13, 17, or 22 had occurred at nonrandom frequencies and in at least one instance of each malignancy grade of adult glioma. The tumors in which loss of constitutional heterozygosity was observed were composed of one or a mixture of glial cell subtypes displaying astrocytic, oligodendrocytic, and/or ependymal differentiation. These results demonstrate a close association of the loss of chromosome 10 sequences with the most malignant histological stage of glioma and that glioblastoma arises as the clonal expansion of an earlier staged precursor. Furthermore they suggest that glioblastoma is a common phenotypic and malignancy terminus for glial tumors of various cellular subtypes which is reached through a common molecular pathway. This approach which involves the identification of malignancy stage specific somatic losses of heterozygosity provides a genotypic, rather than phenotypic, analysis of tumor progression.