Boikos S A, Stratakis C A
Section on Endocrinology and Genetics, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA.
Histol Histopathol. 2008 Jan;23(1):109-16. doi: 10.14670/HH-23.109.
Medullary thyroid carcinoma is the most common cause of death among patients with multiple endocrine neoplasia (MEN) 2. Dominant-activating mutations in the RET proto-oncogene have been shown to have a central role in the development of MEN 2 and sporadic medullary thyroid cancer (MTC): about half of sporadic MTCs are caused by somatic genetic changes of the RET oncogene. Inactivating mutations of the same gene lead to Hirschprung disease and other developmental defects. Thus, RET genetic changes lead to phenotypes that largely depend on their location in the gene and the function and timing of developmental expression of the RET protein. The reproducibility of the phenotype caused by each RET genotype led to MEN 2/MTC being among the first conditions in Medicine where a drastic measure is applied to prevent cancer, following genetic testing: thyroidectomy is currently routinely done in young children that are carriers of MTC-predisposing RET mutations. RET inhibitors have been also developed recently and are used in various types of thyroid and other cancers. This report reviews the RET involvement in the etiology of MEN 2 and MTC and updates the therapeutic approach in preclinical and clinical studies.
甲状腺髓样癌是多发性内分泌腺瘤病（MEN）2患者最常见的死亡原因。RET原癌基因的显性激活突变已被证明在MEN 2和散发性甲状腺髓样癌（MTC）的发生发展中起核心作用：约一半的散发性MTC是由RET癌基因的体细胞遗传改变引起的。同一基因的失活突变会导致先天性巨结肠病和其他发育缺陷。因此，RET基因改变导致的表型很大程度上取决于其在基因中的位置以及RET蛋白发育表达的功能和时间。每种RET基因型所导致表型的可重复性使得MEN 2/MTC成为医学上最早在基因检测后采取严厉措施预防癌症的病症之一：目前，对于携带易患MTC的RET突变的幼儿，常规会进行甲状腺切除术。最近也开发了RET抑制剂，并用于各种类型的甲状腺癌和其他癌症。本报告回顾了RET在MEN 2和MTC病因学中的作用，并更新了临床前和临床研究中的治疗方法。
