Duerr E M, Rollbrocker B, Hayashi Y, Peters N, Meyer-Puttlitz B, Louis D N, Schramm J, Wiestler O D, Parsons R, Eng C, von Deimling A
Department of Neuropathology, University of Bonn Medical Center, Germany.
Oncogene. 1998 Apr 30;16(17):2259-64. doi: 10.1038/sj.onc.1201756.
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 were 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.
细胞遗传学和杂合性缺失研究表明，10号染色体上至少存在一个与高级别胶质瘤形成有关的肿瘤抑制基因。最近，已在染色体带10q23上鉴定出PTEN基因，也称为MMAC1或TEP1。初步研究揭示了在有限系列的胶质瘤细胞系和成胶质细胞瘤中PTEN存在突变。为了系统评估PTEN在胶质瘤中的作用，我们通过单链构象多态性（SSCP）和直接测序分析了331例胶质瘤和神经胶质神经元肿瘤中整个PTEN编码序列。在20/142例成胶质细胞瘤、1/7例巨细胞成胶质细胞瘤、1/2例胶质肉瘤、1/30例毛细胞型星形细胞瘤和2/22例少突胶质细胞瘤中检测到PTEN突变。在52例星形细胞瘤、37例少突星形细胞瘤、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例神经节胶质瘤和1例胚胎发育不良性神经上皮肿瘤中未检测到PTEN突变。此外，检查了所有肿瘤中PTEN基因纯合缺失情况；在7例无PTEN突变的成胶质细胞瘤中检测到纯合缺失。因此，PTEN突变约见于20%的成胶质细胞瘤，但在低级别胶质瘤中罕见。这些发现证实PTEN是参与成胶质细胞瘤发生发展的10号染色体肿瘤抑制基因之一。
