PTEN mutations in gliomas and glioneuronal tumors
PTEN mutations in gliomas and glioneuronal tumors
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DOI：
10.1038/sj.onc.1201756
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发表时间：
1998-04-30
期刊：
影响因子：
8
通讯作者：
von Deimling, A
中科院分区：
文献类型：
--
作者：
Duerr, EM;Rollbrocker, B;von Deimling, A
细胞遗传学和杂合性缺失研究表明，在10号染色体上至少存在一个肿瘤抑制基因，参与高级别胶质瘤的形成。最近，已鉴定出位于染色体10 q23带的PTEN基因，也称为MMAC 1或TEP 1。最初的研究揭示了在有限系列的胶质瘤细胞系和胶质母细胞瘤中PTEN的突变。为了系统地评价PTEN在胶质瘤中的参与，我们通过SSCP和直接测序分析了331例胶质瘤和胶质神经元肿瘤中的整个PTEN编码序列。142例胶质母细胞瘤、7例巨细胞胶质母细胞瘤、2例胶质瘤、30例毛细胞型星形细胞瘤和2例少突胶质细胞瘤中仅检测到PTEN突变。52例星形细胞瘤、37例少突胶质细胞瘤、3例室管膜下巨细胞星形细胞瘤、4例多形性黄色星形细胞瘤、15例室管膜瘤、16例神经节细胞胶质瘤和1例胚胎发育不良性神经上皮瘤中未检测到PTEN突变。此外，检查所有肿瘤中是否存在PTEN基因纯合缺失;在7个没有PTEN突变的胶质母细胞瘤中检测到这些缺失。因此，PTEN突变发生在大约20%的胶质母细胞瘤中，但在低级别胶质瘤中很少见。这些发现证实了PTEN是参与胶质母细胞瘤发展的10号染色体肿瘤抑制基因之一。
Cytogenetic and loss of heterozygosity studies have suggested the presence of at least one tumor suppressor gene on chromosome 10 involved in the formation of high grade gliomas, Recently, the PTEN gene, also termed MMAC1 or TEP1, on chromosomal band 10q23 has been identified. Initial studies revealed mutations of PTEN in limited series of glioma cell lines and glioblastomas. In order to systematically evaluate the involvement of PTEN in gliomas, we have analysed the entire PTEN coding sequence by SSCP and direct sequencing in a series of 331 gliomas and glioneuronal tumors. PTEN mutations mere detected in 20/142 glioblastomas, 1/7 giant cell glioblastomas, 1/2 gliosarcomas, 1/30 pilocytic astrocytomas and 2/22 oligodendrogliomas, No PTEN mutations were detected in 52 astrocytomas, 37 oligoastrocytomas, three subependymal giant cell astrocytomas, four pleomorphic xanthoastrocytomas, 15 ependymomas, 16 gangliogliomas and one dysembryoplastic neuroepithelial tumor. In addition, all tumors were examined for the presence of homozygous deletions of the PTEN gene; these were detected in 7 glioblastomas that did not have PTEN mutations. Therefore, PTEN mutations occur in approximately 20% of glioblastomas but are rare in lower grade gliomas, These findings confirm that PTEN is one of the chromosome 10 tumor suppressor genes involved in the development of glioblastomas.