Iyota K, Takeda K, Matsuzuka F, Okabayashi T, Morita S, Kuma K, Hashimoto K
Second Department of Internal Medicine, Kochi Medical School, Nankoku City, Japan.
J Endocrinol Invest. 1994 Nov;17(10):775-82. doi: 10.1007/BF03347774.
Abnormalities of the gene encoding the sequence-specific DNA-binding protein, nuclear phosphorprotein p53, are among the most common genetic alterations observed in human cancers. A mutation of this tumor suppressor gene has been reported with a low prevalence in differentiated thyroid carcinomas, while the prevalence was high in undifferentiated thyroid carcinomas. We used denaturing gradient gel electrophoresis (DGGE) to probe for mutations of p53 gene in order to determine its role in the genesis of malignant thyroid lymphoma. Involvement of 27 samples had been proven by histopathologic examination of specimen obtained by open biopsy of the thyroid gland or from cervical lymph nodes. DNA was extracted from tissues embedded in paraffin blocks and exons 5-8 of p53 gene were examined for the presence of mutations by DGGE following amplification by PCR using GC-clamped primers. To confirm accuracy of the method, samples with known p53 mutations were included in the study. No mutations were detected in any of the amplified exons of malignant thyroid lymphoma samples. These results suggest that p53 mutations are not present or are uncommon in Japanese patients with malignant thyroid lymphomas. The role of p53 in this form of carcinogenesis cannot be fully excluded since we have not examined the occurrence of mutations in regions upstream of exon 5.
编码序列特异性DNA结合蛋白核磷蛋白p53的基因异常，是人类癌症中最常见的基因改变之一。据报道，这种肿瘤抑制基因的突变在分化型甲状腺癌中的发生率较低，而在未分化型甲状腺癌中的发生率较高。我们使用变性梯度凝胶电泳（DGGE）来检测p53基因的突变，以确定其在恶性甲状腺淋巴瘤发生中的作用。通过对甲状腺或颈部淋巴结开放活检获得的标本进行组织病理学检查，已证实27个样本受累。从石蜡包埋的组织中提取DNA，使用GC夹引物进行PCR扩增后，通过DGGE检测p53基因的第5-8外显子是否存在突变。为了确认该方法的准确性，研究中纳入了已知p53突变的样本。在恶性甲状腺淋巴瘤样本的任何扩增外显子中均未检测到突变。这些结果表明，p53突变在日本恶性甲状腺淋巴瘤患者中不存在或不常见。由于我们尚未检测第5外显子上游区域的突变情况，因此不能完全排除p53在这种致癌形式中的作用。
