Mulligan L M, Kwok J B, Healey C S, Elsdon M J, Eng C, Gardner E, Love D R, Mole S E, Moore J K, Papi L
Department of Pathology, University of Cambridge, UK.
Nature. 1993 Jun 3;363(6428):458-60. doi: 10.1038/363458a0.
Multiple endocrine neoplasia type 2A (MEN 2A) is a dominantly inherited cancer syndrome that affects tissues derived from neural ectoderm. It is characterized by medullary thyroid carcinoma (MTC) and phaeochromocytoma. The MEN2A gene has recently been localized by a combination of genetic and physical mapping techniques to a 480-kilobase region in chromosome 10q11.2 (refs 2,3). The DNA segment encompasses the RET proto-oncogene, a receptor tyrosine kinase gene expressed in MTC and phaeochromocytoma and at lower levels in normal human thyroid. This suggested RET as a candidate for the MEN2A gene. We have identified missense mutations of the RET proto-oncogene in 20 of 23 apparently distinct MEN 2A families, but not in 23 normal controls. Further, 19 of these 20 mutations affect the same conserved cysteine residue at the boundary of the RET extracellular and transmembrane domains.
2A型多发性内分泌腺瘤病（MEN 2A）是一种显性遗传的癌症综合征，会影响源自神经外胚层的组织。其特征为甲状腺髓样癌（MTC）和嗜铬细胞瘤。最近，通过基因和物理图谱技术相结合的方法，将MEN2A基因定位到了10号染色体q11.2区域的一个480千碱基的区域（参考文献2,3）。该DNA片段包含RET原癌基因，这是一种受体酪氨酸激酶基因，在MTC和嗜铬细胞瘤中表达，在正常人类甲状腺中的表达水平较低。这表明RET是MEN2A基因的候选基因。我们在23个明显不同的MEN 2A家族中的20个中鉴定出了RET原癌基因的错义突变，但在23个正常对照中未发现。此外，这20个突变中的19个影响RET细胞外和跨膜结构域边界处的同一个保守半胱氨酸残基。
