Low frequency of genetic change in p53 immunopositive clones in human epidermis.-猫眼课题宝

人表皮中 p53 免疫阳性克隆的遗传变化频率较低。

DOI：

10.1038/sj.jid.5600549.x

发表时间：

1999

期刊：

The Journal of investigative dermatology

影响因子：

通讯作者：

中科院分区：

文献类型：

作者：

H. Tabata;T. Nagano;A. Ray;N. Flanagan;M. Birch;J. Rees

白种人暴露在阳光下的皮肤含有数千个p53突变的克隆，这些克隆在临床上是不可见的。使用p53或Ki 67抗原，p53测序，和杂合性丢失分析的整体安装免疫染色，我们进一步确定这些克隆。研究的等位基因的杂合性丢失是罕见的，例外的9 q，这发生在28.3%的样本。P53克隆在基底细胞癌患者中比对照组更常见且更大（p < 0.03）。杂合性缺失在来自基底细胞癌个体的克隆中也比来自没有基底细胞癌病史的受试者的克隆中更常见，如果两者都与紫外线辐射暴露有关，则可以预期。克隆的p53测序与紫外线辐射的诱变作用一致。令人惊讶的是，与光化性角化病或基底细胞癌的情况不同，发现含有p53克隆的皮肤没有显示Ki 67阳性细胞簇。这些结果表明，在人类皮肤中，p53突变与基因组不稳定性或异常细胞周期没有直接关系; p53免疫阳性克隆要么在遗传上是不同的，要么是其他皮肤鳞状细胞病变的前体; p53免疫阳性克隆是早期病变，因为还没有发生增殖的总体障碍。

Sun-exposed skin of Caucasians harbors thousands of p53-mutated clones, which are clinically invisible. Using whole mount immunostaining for p53 or Ki67 antigens, p53 sequencing, and loss of heterozygosity analysis, we have further characterised these clones. Loss of heterozygosity for the alleles examined is uncommon with the exception of 9q, which occurred in 28.3% of the samples. P53 clones are more common and larger in individuals with basal cell carcinoma than in control subjects (p < 0.03). Loss of heterozygosity is also more common in clones from individuals with basal cell carcinoma than in clones from subjects without a history of basal cell carcinoma, as would be expected if both relate to ultraviolet radiation exposure. p53 sequencing of clones is in keeping with the mutagenic role of ultraviolet radiation. Surprisingly, skin found to harbor p53 clones showed no clusters of Ki67 positive cells, unlike the situation for actinic keratoses or basal cell carcinomas. These results show that in human skin p53 mutation is not directly associated with genomic instability or abnormal cell cycling; that the p53 immunopositive clones are either genetically distinct or precursors to other squamous cell lesions of skin; and that p53 immunopositive clones are early lesions, in that gross disturbance of proliferation has not already occurred.