GENE P53 MUTATIONS ARE RESTRICTED TO POORLY DIFFERENTIATED AND UNDIFFERENTIATED CARCINOMAS OF THE THYROID-GLAND
GENE P53 MUTATIONS ARE RESTRICTED TO POORLY DIFFERENTIATED AND UNDIFFERENTIATED CARCINOMAS OF THE THYROID-GLAND
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DOI：
10.1172/jci116385
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发表时间：
1993-04-01
影响因子：
15.9
通讯作者：
PIEROTTI, MA
中科院分区：
文献类型：
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作者：
DONGHI, R;LONGONI, A;PIEROTTI, MA
应用分子生物学和免疫细胞化学相结合的方法，对52例不同类型甲状腺癌的肿瘤标本进行了p53基因分析。组织学类型包括37例高分化乳头状和滤泡状癌，8例低分化癌和7例未分化癌。单链构象多态性分析表明，p53基因在所有分化的肿瘤中不受影响。然而，在八分之二（25%）的低分化癌和七分之五（71%）的未分化癌中，p53突变被鉴定，随后通过DNA测序进行表征。1例未分化癌显示两个不同程度分化的区域。比较分析的p53基因，在这一肿瘤的分化程度较高和较低的地区，清楚地表明，p53突变仅限于肿瘤标本的后一个组成部分。这些结果表明，p53基因的突变与甲状腺肿瘤的最具侵略性的组织学类型，如未分化癌，并在一定程度上，低分化癌，该基因的改变代表了人类甲状腺癌发生的晚期遗传事件。
The p53 gene was analyzed in tumor specimens obtained from 52 patients with various types of carcinoma of the thyroid gland by a combined molecular and immunocytochemical approach. The histologic types included 37 well-differentiated papillary and follicular carcinomas, 8 poorly differentiated, and 7 undifferentiated carcinomas. The p53 gene was shown to be unaffected in all differentiated tumors by single-strand conformation polymorphism analysis. However, in two out of eight (25%) of poorly differentiated carcinomas and five out of seven (71%) undifferentiated carcinomas, p53 mutations were identified and subsequently characterized by DNA sequencing. One undifferentiated carcinoma displayed two areas with varying degrees of differentiation. The comparative analysis of the p53 gene, in both the more and the less differentiated area of this tumor, clearly showed that the p53 mutation was confined to the latter component of the tumor specimen. These results indicate that mutations of the p53 gene are associated with the most aggressive histologic types of thyroid tumors, such as the undifferentiated carcinoma and, to a certain extent, the poorly differentiated carcinoma, and that the alterations of this gene represent a late genetic event in human thyroid carcinogenesis.