Mutational profile of the PTEN gene in primary human astrocytic tumors and cultivated xenografts
Mutational profile of the PTEN gene in primary human astrocytic tumors and cultivated xenografts
复制标题
DOI：
10.1097/00005072-199911000-00007
复制
发表时间：
1999-11-01
影响因子：
3.2
通讯作者：
Collins, VP
中科院分区：
文献类型：
--
作者：
Schmidt, EE;Ichimura, K;Collins, VP
胶质母细胞瘤中最常见的遗传异常是10号染色体上等位基因的丢失。我们对10 q23上的PTEN抑癌基因进行了全面的研究，包括杂合性丢失（洛）分析、多重PCR、突变分析和逆转录PCR（RT-PCR）。总共分析了151个胶质母细胞瘤、41个间变性星形细胞瘤、15个星形细胞瘤和13个神经胶质瘤细胞系以及23个源自原发性胶质母细胞瘤的异种移植物，这允许比较原发性肿瘤与异种移植物中的PTEN基因状态。在7%的胶质母细胞瘤中发现了纯合子缺失，40%的胶质母细胞瘤显示了单个保留等位基因的突变。这种突变频率高于以前报道的。鉴定的大量突变允许沿着编码序列呈现突变谱沿着。大多数突变似乎影响保守残基或结构保守区域。在异种移植物中选择了PTEN改变，并且有证据表明它们甚至可以促进异种移植物的建立。在星形细胞瘤中没有发现改变，只有5%的间变性星形细胞瘤有突变。因此，野生型PTEN的缺失代表了与星形细胞肿瘤进展为胶质母细胞瘤相关的主要异常之一，并且当在异种移植物中培养胶质母细胞瘤组织时提供了强的选择性生长优势。与EGFR扩增无明显相关性。
The genetic abnormality most frequently identified in glioblastomas is loss of alleles on chromosome 10. We have performed a comprehensive study of the PTEN tumor suppressor gene on 10q23, including loss of heterozygosity (LOH) analysis, multiplex PCR, mutation analysis, and reverse transcription PCR (RT-PCR). In total, 151 glioblastomas, 41 anaplastic astrocytomas, 15 astrocytomas, and 13 glioma cell Lines were analyzed as well as 23 xenografts derived from primary glioblastomas, which allows a comparison of the PTEN gene status in primary tumors versus xenografts. Homozygous deletions were found in 7% of the glioblastomas and 40% showed mutation of a single retained allele. This mutation frequency is higher than reported previously. The large number of mutations identified allows the presentation of a mutational profile along the coding sequence. The majority of mutations appear to affect conserved residues or structurally conserved regions. PTEN alterations were selected for in xenografts, and there is evidence that they may even facilitate establishment of xenografts. No alterations were found in astrocytomas and only 5% of anaplastic astrocytomas had mutations. Thus, loss of wild type PTEN represents one of the major abnormalities associated with astrocytic tumor progression to glioblastoma and provides a strong selective growth advantage when cultivating glioblastoma tissue in xenografts. No correlation with EGFR amplification was evident.