A novel case of multiple endocrine neoplasia type 2A associated with two de novo mutations of the RET protooncogene
A novel case of multiple endocrine neoplasia type 2A associated with two de novo mutations of the RET protooncogene
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DOI：
10.1210/jc.84.10.3522
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发表时间：
1999-10-01
影响因子：
5.8
通讯作者：
Colantuoni, V
中科院分区：
文献类型：
--
作者：
Tessitore, A;Sinisi, AA;Colantuoni, V
我们报告了一例与原癌基因 RET 的两个突变相关的 2A 型多发性内分泌肿瘤 (MEN 2A) 的新病例。其中一个影响密码子 634 并导致半胱氨酸替换为精氨酸；第二个位于密码子 640 处，导致跨膜区域中丙氨酸被甘氨酸取代。这两种突变存在于相同的 RET 等位基因上，并在种系和肿瘤 DNA 中检测到。这两种突变都是从头突变的，即在父母或亲戚的 DNA 中没有发现它们。免疫组织化学和 RT-PCR 分析表明，嗜铬细胞瘤表达降钙素以及两个 RET 等位基因。从肿瘤中建立并在培养物中增殖的细胞系维持了 RET 和降钙素的表达，就像最初的嗜铬细胞瘤一样。由于该患者患有甲状腺髓样癌和嗜铬细胞瘤，但没有甲状旁腺受累，因此我们推测该临床表现可能与两种 RET 突变和异常降钙素的产生有关。这是首次报告 MEN 2A 病例，该病例由 RET 基因的两个突变引起，并与产生降钙素的嗜铬细胞瘤相关。
We report a novel case of multiple endocrine neoplasia type 2A (MEN 2A) associated with two mutations of the protooncogene RET. One affects codon 634 and causes a cysteine to arginine substitution; the second at codon 640 causes an alanine to glycine substitution in the transmembrane region. The two mutations were present on the same RET allele and were detected in germline and tumor DNA. Both mutations were de novo, i.e. they were not found in the DNA of the parents or relatives. Immunohistochemical and RT-PCR analysis showed that the pheochromocytoma expressed calcitonin as well as both RET alleles. A cell line established from the tumor and propagated in culture sustained the expression of RET and calcitonin, as did the original pheochromocytoma. Because the patient presented with medullary thyroid carcinoma and pheuchromocytoma without parathyroid gland involvement, we speculate that this clinical picture could be correlated with the two RET mutations and to the unusual calcitonin production. This is the first report of a MEN 2A case due to two mutations of the RET gene and associated with a calcitonin-producing pheochromocytoma.