Santoro M, Carlomagno F, Romano A, Bottaro D P, Dathan N A, Grieco M, Fusco A, Vecchio G, Matoskova B, Kraus M H
Centro di Endocrinologia ed Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (CNR), Napoli, Italy.
Science. 1995 Jan 20;267(5196):381-3. doi: 10.1126/science.7824936.
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.
2A型和2B型多发性内分泌肿瘤（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。这三种综合征均与RET基因突变有关，RET基因编码一种受体样酪氨酸激酶。由于RET激酶的组成性激活，改变后的RET等位基因在NIH 3T3细胞中显示为转化基因。MEN2A突变导致RET在稳态下二聚化，而MEN2B突变在数量和质量上均改变了RET的催化特性。在这些肿瘤综合征中RET的致癌转化确立了人类癌症中显性转化基因的种系传递。
