脑肿瘤中p53基因突变的研究

应用ＰＣＲＳＳＣＰ技术及ＤＮＡ 测序技术对３７ 例原发性脑肿瘤及相应外周血淋巴细胞中ｐ５３ 基因５ ～８ 外显子的突变情况进行了检测，结果表明，ｐ５３ 基因在原发性脑肿瘤中的突变频率为１９ ％ （７／３７） ．并且突变频率在不同病理类别脑肿瘤中的分布是非随机的，其中星形细胞肿瘤中的突变频率最高，为３６ ％ （５／１４） ．所有突变均为错义点突变，５７ ％ （４／７） 的突变位于ＣｐＧ位点．突变仅发现于脑组织中，外周血淋巴细胞中未检出突变，这些结果提示，ｐ５３ 基因突变在脑肿瘤的发生发展过程中起一定的作用，ｐ５３ 基因在散发性脑肿瘤中的突变为体细胞型的突变

DETECTION OF p53 TUMOR SUPPRESSOR GENE MUTATION IN HUMAN BRAIN TUMORS

To search the p53 mutations in human brain tumors, mutations in the conserved regions of p53 gene were investigated in 37 human brain tumors by polymerase chain reaction single strand conformation polymorphism (PCR SSCP) analysis.7 cases were found to have putative p53 mutations. Direct sequencing of polymerase chain reaction amplified DNA from these 7 cases confirmed the presence of different point mutations. The mutations did not follow a random distribution among the various different subtypes, but occurred in 36%(5/14) of astrocytomas, 9%(2/23) of non astrocytic primary brain tumors. All mutations were missense ones and 57% occurred at sites of CpG dinucleotide. p53 mutations were not detected in any of the 37 leukocyte DNA samples from patients with brain tumors. These results suggest that the mutations of p53 gene may play a role in the development of many human brain tumors; p53 gene mutations in sporadic human brain tumors are somatic in origin (i.e., nonprenatally determined).