Mutation of RET proto-oncogene in Families of multiple endocrine neoplasia type 2

2型多发性内分泌肿瘤家系RET原癌基因突变

• 批准号: 07671332
• 负责人: TAKAMI Hiroshi
• 金额: $ 1.47万
• 依托单位: Teikyo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671332/
• 关键词: multiple endocrine; neoplasia; RET proto-oncogen; genetic test; 多発性内分泌腫瘍症2型; 家族性髄様癌

Multiple endocrine neoplasia types 2A and 2B (MEN 2A and 2B) and familial or sporadic medullary thyroid carcinomas (MTC) are associated with mutations in the RET proto-oncogene located at chromosome 10q11.2. We investigated the spectrum of RET mutations among Japanese patlents with these diseased (representatives of 39 families with MEN2 or FMTC,and 33 sporadic MTCs). Mutations in nucleotide sequences encoding one of three specific cyteine residues in the extracellular domain of RET protein were found in 31 of the 32 MEN2A patients and all three FMTC patients examined. A mutation at codon 918, causing the substitution of threonine for methionine in the tyrosine kinase domain of the protein, was found in germline DNAs of all four patients with MEN2B and in 7 of the 33 sporadic MTCs. Germline mutations of codon 768, GAG to GAC (Glu to Asp), were detected in two patients with sporadic MTCs. We also identified two novel somatic mutations in sporadic MTCs, one at codon 631 (Asp to Gly) and the other at codon 634 (Cys to Arg). These two mutations will contrlbute to study functional domains of the RET protein.

多种内分泌肿瘤2a和2b（男性2a和2b）以及家族性或零星甲状腺癌（MTC）与位于10q11.2染色体的Ret原癌基因的突变有关。我们调查了这些患病的日本专利专利群中的RET突变的范围（39家有MEN2或FMTC的家族的代表和33个零星MTC）。在32例MEN2A患者中的31例和所有三名FMTC患者中，发现了编码RET蛋白的三个特异性Cyteine残基之一的核苷酸序列中的突变。在蛋白质的酪氨酸激酶结构域中替代了苏氨酸在蛋白质的酪氨酸激酶结构域中替代苏氨酸的一个突变，在所有四个MEN2B患者的生殖线DNA中发现，在33个零星MTC中的7例中发现了蛋氨酸。在两名零星MTC患者中检测到密码子768的生殖线突变，GAG至GAC（GLU至ASP）。我们还确定了零星MTC中的两个新型体细胞突变，一个在密码子631（ASP到Gly），另一个在密码子634（cys to arg）上。这两个突变将相反，以研究RET蛋白的功能结构域。

项目成果

Takami H: "Familial medullary thyroid carcinoma unassociated with multiple endocrine neoplasia" Thyroidology Exp Clim. 8. 9-14 (1996)

Takami H：“与多发性内分泌肿瘤无关的家族性甲状腺髓样癌”甲状腺学实验气候。

Takami H: "Cuncurrent diagnosis and treatment of medullary thyroid carcinoma" Thyroidology Exp Cli. 8. 35-39 (1996)

Takami H：“甲状腺髓样癌的并发诊断和治疗” Thyroidology Exp Cli。

Takami,H.: "Current daignosis and tratment of medullary thyroid caroinoma" Thyroidology Exp Clin. 8. 35-39 (1996)

Takami,H.：“甲状腺髓样癌的当前诊断和治疗”甲状腺学实验临床。

Takami,H.: "Familial medullary thyroid carcinoma unassociated with multiple endocrine neoplasia" Thyroidology Ecp Clim. 8. 9-14 (1996)

Takami,H.：“与多发性内分泌肿瘤无关的家族性甲状腺髓样癌”甲状腺学 Ecp Clim。

Takami,H,: "Familial medullary thyrid carcinoma unassociated with multiple endocrine neoplasia" Thyroidology Exp Ciln. 8. 9-14 (1996)

Takami，H：“与多发性内分泌肿瘤无关的家族性甲状腺髓样癌”甲状腺学实验。