Mashiyama S, Murakami Y, Yoshimoto T, Sekiya T, Hayashi K
Oncogene Division, National Cancer Center Research Institute, Tokyo, Japan.
Oncogene. 1991 Aug;6(8):1313-8.
Single-strand conformation polymorphism analysis of polymerase chain reaction products (PCR-SSCP analysis) was used for detection of mutations of the p53 gene in surgical specimens of human brain tumors. Six of 45 brain tumors showed mobility shifts in the analyses. These six tumors also showed loss of a normal allele. The samples were examined further by direct sequencing. Results showed that four of them had single-base substitutions and the other two had deletions of one and eight base pairs. Five of the six mutations detected were clustered in highly conserved regions of the p53 gene. The frequency of p53 gene mutations in primary brain tumors examined was 9.8%. We also found two new polymorphic markers in the p53 gene, one in intron 7 and the other in an Alu repeat in exon 11. Both markers could be detected by SSCP analysis. Using these two markers, we found two cases of loss of heterozygosity in other brain tumor specimens. Results suggested that aberrations of the p53 gene were not correlated with the malignancy of some types of brain tumors such as anaplastic astrocytoma and glioblastoma, contrary to previous observations on colorectal cancers.
采用聚合酶链反应产物单链构象多态性分析（PCR - SSCP分析）检测人脑肿瘤手术标本中p53基因的突变情况。45例脑肿瘤中有6例在分析中出现迁移率改变。这6例肿瘤还显示一个正常等位基因缺失。通过直接测序对样本进行进一步检测。结果显示，其中4例有单碱基替换，另外2例分别缺失1个和8个碱基对。检测到的6个突变中有5个集中在p53基因的高度保守区域。所检测的原发性脑肿瘤中p53基因突变频率为9.8%。我们还在p53基因中发现了两个新的多态性标记，一个在内含子7中，另一个在外显子11的一个Alu重复序列中。这两个标记均可通过SSCP分析检测到。利用这两个标记，我们在其他脑肿瘤标本中发现了2例杂合性缺失。结果表明，与之前对结直肠癌的观察结果相反，p53基因的畸变与某些类型的脑肿瘤如间变性星形细胞瘤和胶质母细胞瘤的恶性程度无关。
