Molecular analysis of the TSC1 and TSC2 tumour suppressor genes in sporadic glial and glioneuronal tumours
Molecular analysis of the TSC1 and TSC2 tumour suppressor genes in sporadic glial and glioneuronal tumours
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DOI：
10.1007/s004390000390
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发表时间：
2000-10-01
期刊：
影响因子：
5.3
通讯作者：
Cheadle, JP
中科院分区：
文献类型：
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作者：
Parry, L;Maynard, JH;Cheadle, JP
据报道，在散发性星形细胞瘤中TSC 2肿瘤抑制基因产物tuberin表达减少，表明TSC基因可能在形成散发性胶质细胞或胶质神经元中发挥作用。我们研究了配对的宪法和肿瘤DNA样本，从100例散发性胶质细胞和胶质神经元肿瘤的杂合性丢失（洛）在TSCI和TSC 2位点使用7个以前报道的和7个新的多态性标记的组合。洛缺失见于1/16例星形细胞瘤、3/15例室管膜瘤、5/16例神经节细胞胶质瘤、2/14例多形性胶质母细胞瘤、0/7例少突胶质细胞瘤、0/7例少突/星形细胞混合型肿瘤、2/11例毛细胞型星形细胞瘤和室管膜下巨细胞星形细胞瘤。然而，在显示洛缺失的肿瘤中TSCI或TSC 2基因的所有编码外显子以及21个神经节细胞胶质瘤中这两个基因的SSCP筛选显示没有基因内突变。缺乏可证明的失活的两个等位基因的任一TSC基因在任何肿瘤的调查表明，他们不发挥经常的作用，在病因学的散发性神经胶质或胶质神经元肿瘤。
Reduced expression of the TSC2 tumour suppressor gene product, tuberin, has been reported in sporadic astrocytomas, suggesting that the TSC genes may in formation of sporadic glial or glioneuronal play a role In tumours. We studied paired constitutional and tumour DNA samples from 100 patients with sporadic glial and glioneuronal tumours for loss of heterozygosity (LOH) at the TSCI and TSC2 loci using a combination of seven previously reported and seven novel polymorphic markers. LOH was seen in 1/16 astrocytomas, 3/15 ependymomas, 5/16 gangliogliomas, 2/14 glioblastoma multiforme, 0/7 oligodendrogliomas, 0/7 tumours of mixed oligodendrocytic/astrocytic histology, 2/11 pilocytic astrocytomas and 0/1 subependymal giant cell astrocytomas informative at both loci. However, SSCP screening of all coding exons of the TSCI or TSC2 genes in the tumours displaying LOH, and of both genes in 21 gangliogliomas, revealed no intragenic mutations. The lack of demonstrable inactivation of both alleles of either TSC gene in any of the tumours investigated suggests that they do not play a frequent role in the aetiology of sporadic glial or glioneuronal tumours.