P53-GENE MUTATIONS ASSOCIATED WITH ANAPLASTIC TRANSFORMATION OF HUMAN THYROID CARCINOMAS

被引:119
作者
NAKAMURA, T
YANA, I
KOBAYASHI, T
SHIN, E
KARAKAWA, K
FUJITA, S
MIYA, A
MORI, T
NISHISHO, I
TAKAI, S
机构
[1] OSAKA UNIV, SCH MED,BIOMED RES CTR,DEPT MED GENET, DIV CLIN GENET,2-2 YAMADAOKA, SUITA, OSAKA 565, JAPAN
[2] OSAKA UNIV, SCH MED, DEPT SURG 2, FUKUSHIMA KU, OSAKA 553, JAPAN
来源
JAPANESE JOURNAL OF CANCER RESEARCH | 1992年 / 83卷 / 12期
关键词
P53-GENE; ANAPLASTIC THYROID CARCINOMA; PROGRESSION; RNASE PROTECTION ANALYSIS;
D O I
10.1111/j.1349-7006.1992.tb02761.x
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Anaplastic carcinoma of the thyroid gland, which is one of the most aggressive, malignant tumors in humans, is considered to originate from preexisting differentiated thyroid cancer. To define the genetic alterations associated with such progression, we examined nine cases of anaplastic thyroid carcinoma for mutation in exons 4-9 of the p53 tumor suppressor gene. Preliminary screening for mutation by RNase protection analysis demonstrated that two out of nine anaplastic carcinomas contained sequence alterations in the p53 gene. Subsequent DNA sequencing identified the mutated nucleotides in these two cases; one was a nonsense mutation at codon 165, and the other was a single-base deletion at codon 176 resulting in the creation of a stop codon downstream due to frameshift. The fact that no mutations were detected in coexisting foci of papillary carcinomas from the same patients shows that these mutations of the p53 gene occurred after development of papillary carcinomas. These results suggest that p53 gene mutation triggers the progression from differentiated into anaplastic carcinoma in the human thyroid gland.
引用
收藏
页码:1293 / 1298
页数:6
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