Watanabe K, Peraud A, Gratas C, Wakai S, Kleihues P, Ohgaki H
Unit of Molecular Pathology, International Agency for Research on Cancer, Lyon, France.
Acta Neuropathol. 1998 Jun;95(6):559-64. doi: 10.1007/s004010050840.
The gemistocytic astrocytoma is a histological variant of diffuse astrocytomas and is characterised by the presence of large, GFAP-expressing neoplastic astrocytes (gemistocytes) and a tendency towards rapid progression to glioblastoma. In this study, we analyzed 28 gemistocytic astrocytomas (mean fraction of gemistocytes, 35.0+/-9.9%) for mutations in the p53 and PTEN (MMAC1) tumour suppressor genes. Single strand conformation polymorphism (SSCP), followed by direct DNA sequencing of p53 exons 5-8, revealed a mutation in 23 of 28 (82%) cases. Regional analysis of four tumours revealed identical p53 mutations in gemistocytic and fibrillary tumour areas. In contrast, none of 15 gemistocytic astrocytomas (WHO Grade II) and only two of 11 (18%) anaplastic gemistocytic astrocytomas (WHO Grade III) contained a PTEN mutation. Of these, one was a 1 bp deletion in codon 345 and the other a 1 bp insertion in intron 4. Differential PCR did not reveal homozygous PTEN deletion in any of the tumours analysed. These results indicate that p53 mutations are a genetic hallmark of gemistocytic astrocytomas, whilst PTEN mutations are absent in low-grade and rare in anaplastic gemistocytic astrocytomas.
肥胖型星形细胞瘤是弥漫性星形细胞瘤的一种组织学变体，其特征是存在大量表达胶质纤维酸性蛋白（GFAP）的肿瘤性星形胶质细胞（肥胖细胞），且有迅速进展为胶质母细胞瘤的倾向。在本研究中，我们分析了28例肥胖型星形细胞瘤（肥胖细胞的平均比例为35.0±9.9%）的p53和PTEN（MMAC1）肿瘤抑制基因的突变情况。采用单链构象多态性（SSCP）分析，随后对p53基因外显子5至8进行直接DNA测序，结果显示28例中有23例（82%）发生了突变。对4例肿瘤的区域分析显示，肥胖型和纤维型肿瘤区域存在相同的p53突变。相比之下，15例肥胖型星形细胞瘤（WHO二级）均未检测到PTEN突变，11例间变性肥胖型星形细胞瘤（WHO三级）中只有2例（18%）检测到PTEN突变。其中1例为密码子345处1个碱基缺失，另1例为内含子4处1个碱基插入。差异PCR分析未在任何分析的肿瘤中发现PTEN纯合缺失。这些结果表明，p53突变是肥胖型星形细胞瘤的遗传特征，而PTEN突变在低级别肥胖型星形细胞瘤中不存在，在间变性肥胖型星形细胞瘤中罕见。
