P53 gene mutations in pituitary carcinomas
P53 gene mutations in pituitary carcinomas
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DOI：
10.1007/s12022-007-9006-y
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发表时间：
2007-12-01
影响因子：
4.4
通讯作者：
Lloyd, Ricard V.
中科院分区：
文献类型：
--
作者：
Tanizaki, Yoshinori;Jin, Long;Lloyd, Ricard V.
尽管免疫组织化学检测到p53在垂体腺瘤和癌中过度表达已有报道，但之前在这些肿瘤中尚未检测到p53基因的基因突变。我们通过免疫组织化学、聚合酶链式反应扩增以及 p53 外显子 5 至外显子 8 的基因突变测序分析了一系列 8 例垂体腺瘤和 6 例垂体癌。三种癌症的肿瘤细胞中 p53 蛋白的表达超过 20%。其中一个 p53 蛋白过度表达 60% 的肿瘤在密码子 248 处发生突变，这是 p53 突变的常见“热点”，而另一种 p53 蛋白过度表达 90% 的肿瘤在密码子 135 处发生突变。所有腺瘤的 p53 突变均为阴性，并且有 15% 的细胞表达 p53 蛋白。对对照肿瘤（包括四种已证实具有 p53 突变的肺癌）的分析也显示，超过 85% 的肿瘤细胞过度表达 p53 蛋白。具有已知 p53 突变的两种乳腺癌细胞系 MBA-MD 231 和 MBA-MD-486 也显示出超过 85% 的肿瘤细胞过表达 p53。这些结果表明，p53 突变存在于垂体癌的一个亚型中，并且通常与高比例的肿瘤细胞过表达 p53 蛋白相关。
Although p53 overexpression detected by immunohistochemistry has been reported in pituitary adenomas and carcinomas, genetic mutations in the p53 gene have not been previously detected in these tumors. We analyzed a series of eight pituitary adenomas and six pituitary carcinomas by immunohistochemistry, polymerase chain reaction amplification, and sequencing of p53 exon 5 through exon 8 for genetic mutations. Three carcinomas showed more than 20% expression of p53 protein in the tumor cells. One of these tumors with 60% overexpression of p53 protein had a mutation in codon 248, a common "hot spot" for p53 mutation, while the other carcinoma with 90% overexpression of p53 protein had a mutation in codon 135. All adenomas were negative for p53 mutations and had 15% of the cells expressing the p53 protein. Analysis of control tumors including four lung carcinomas with proven p53 mutations also had greater than 85% of the tumor cells overexpressing p53 protein. Two breast carcinoma cell lines with known p53 mutations, MBA-MD 231 and MBA-MD-486, also showed greater than 85% of the tumor cells overexpressing p53. These results show that p53 mutations are present in a subset of pituitary carcinomas and are usually associated with a high percentage of tumor cells overexpressing the p53 protein.