p53 mutations are associated with 17p allelic loss in grade II and grade III astrocytoma.
p53 mutations are associated with 17p allelic loss in grade II and grade III astrocytoma.
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发表时间：
1992-05
期刊：
影响因子：
11.2
通讯作者：
A. Deimling;R. Eibl;H. Ohgaki;D. Louis;K. Ammon;I. Petersen;I. Petersen;P. Kleihues;R. Chung;Otmar D. Wiestler;B. Seizinger
中科院分区：
文献类型：
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作者：
A. Deimling;R. Eibl;H. Ohgaki;D. Louis;K. Ammon;I. Petersen;I. Petersen;P. Kleihues;R. Chung;Otmar D. Wiestler;B. Seizinger
在大约40%的人类星形细胞瘤（WHO II级和III级）和大约30%的多形性胶质母细胞瘤（WHO IV级）病例中观察到17号染色体短臂上的遗传物质丢失。以前的研究表明，多形性胶质母细胞瘤的p53基因，位于17号染色体的短臂，经常在这些胶质母细胞瘤突变。为了探讨低级别星形细胞瘤是否也与相应的p53基因突变相关，我们研究了22例WHO II级和III级星形细胞瘤染色体17 p杂合性丢失和p53突变。p53基因保守区的突变通过外显子5、6、7和8的单链构象多态性分析鉴定，并通过聚合酶链反应产物的直接DNA测序进行验证。在8例II级星形细胞瘤中有3例和14例II级星形细胞瘤中有4例观察到p53突变。在所有22例肿瘤中，通过限制性片段长度多态性分析研究了17号染色体短臂的等位基因丢失。一半的II级星形细胞瘤（4/8）和III级星形细胞瘤（7/14）表现出染色体17 p等位基因丢失。p53基因的突变仅在17 p等位基因缺失的肿瘤中观察到。我们的研究结果表明，p53突变并不局限于多形性胶质母细胞瘤，可能是重要的低级别星形细胞瘤的肿瘤发生和p53突变在低级别星形细胞瘤与染色体17 p的丢失。这些发现与WHO II级和III级星形细胞瘤肿瘤发生中p53的隐性作用机制一致。
Loss of genetic material on the short arm of chromosome 17 is observed in approximately 40% of human astrocytomas (WHO grades II and III) and in approximately 30% of cases of glioblastoma multiforme (WHO grade IV). Previous studies of glioblastoma multiforme have shown that the p53 gene, located on the short arm of chromosome 17, is frequently mutated in these glioblastomas. To explore whether lower-grade astrocytomas are also associated with corresponding mutations of the p53 gene, we have investigated a series of 22 human astrocytomas of WHO grades II and III both for loss of heterozygosity on chromosome 17p and for p53 mutations. Mutations in the conserved regions of the p53 gene were identified by single strand conformation polymorphism analysis of exons 5, 6, 7, and 8 and were verified by direct DNA sequencing of the polymerase chain reaction products. p53 mutations were observed in 3 of 8 grade II astrocytomas and 4 of 14 grade II astrocytomas. In all 22 tumors, allelic loss of the short arm of chromosome 17 was investigated by restriction fragment length polymorphism analysis. One-half of the grade II astrocytomas (4 of 8) and grade III astrocytomas (7 of 14) exhibited allelic loss on chromosome 17p. Mutations in the p53 gene were exclusively observed in tumors with allelic loss on 17p. Our results show that p53 mutations are not restricted to glioblastoma multiforme and may be important in the tumorigenesis of lower-grade astrocytomas and that p53 mutations in lower-grade astrocytomas are associated with loss of chromosome 17p. These findings are consistent with a recessive mechanism of action of p53 in WHO grade II and III astrocytoma tumorigenesis.