MEN2A 和 MEN2B 的种系突变将 RET 激活为显性转化基因

IF 44.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Pub Date : 1995-01-20 DOI:10.1126/science.7824936

Massimo Santoro, Francesca Carlomagno, Alfredo Romano, Donald P. Bottaro, Nina A. Dathan, Michele Grieco, Alfredo Fusco, Giancarlo Vecchio, Brona Matoskova, Matthias H. Kraus, Pier Paolo Di Fiore

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引用次数: 833

摘要

多发性内分泌肿瘤 2A 型和 2B 型（MEN2A 和 MEN2B）以及家族性甲状腺髓样癌是显性遗传的癌症综合征。这三种综合征都与编码受体样酪氨酸激酶的 RET 基因突变有关。研究表明，RET等位基因的改变是NIH 3T3细胞中的转化基因，是RET激酶组成性激活的结果。MEN2A 基因突变导致 RET 在稳定状态下二聚化，而 MEN2B 基因突变则从数量和质量上改变了 RET 的催化特性。在这些肿瘤综合征中，RET的致癌转化确定了人类癌症中显性转化基因的种系传递。

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Activation of RET as a Dominant Transforming Gene by Germline Mutations of MEN2A and MEN2B

Multiple endocrine neoplasia types 2A and 2B (MEN2A and MEN2B) and familial medullary thyroid carcinoma are dominantly inherited cancer syndromes. All three syndromes are associated with mutations in RET, which encodes a receptor-like tyrosine kinase. The altered RET alleles were shown to be transforming genes in NIH 3T3 cells as a consequence of constitutive activation of the RET kinase. The MEN2A mutation resulted in RET dimerization at steady state, whereas the MEN2B mutation altered RET catalytic properties both quantitatively and qualitatively. Oncogenic conversion of RET in these neoplastic syndromes establishes germline transmission of dominant transforming genes in human cancer.

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来源期刊

Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

审稿时长

2.1 months

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