Pre-symptomatic diagnosis and clinical assessment of genetic analysis for familial endocrine tumors

1.内分泌肿瘤MAN-1基因的分析根据本项目的初步目标，我研究了散发性内分泌肿瘤MAN-1基因的异常。散发性内分泌肿瘤的MENS-1基因突变发生率很低，提示肿瘤的发生机制与家族性内分泌肿瘤不同。结论：1.由于MENS-1基因不是散发性内分泌肿瘤的致病基因，因此利用基因诱导技术不可能产生内分泌肿瘤。家族性甲状腺髓样癌(FMTC)ret癌基因的遗传学研究我研究了两个FMTC家族和一个男性IIA家族。家系A涉及三名甲状腺髓样癌患者和两名携带者，被诊断为携带RET密码子609突变的FMTC。这个家族中的MTC进展非常缓慢。这个家族的临床策略是对发展为MTC的患者进行全甲状腺切除术。B家族包括两名MTC患者和两名携带者，也被诊断为FMTC带有RET密码子620突变。家系C包括5名MTC患者、1名嗜铬细胞瘤患者和2名携带者，被诊断为携带RET密码子634突变的MENS-IIA。我将根据日本厚生劳动省的指导方针对这三个家庭成员进行进一步的研究。

1. Analyses of MEN-1 gene for endocrine tumorsAccoriding to the initial aim of this project, I studied abnormalities of MEN-1 gene for sporadic endoctrine tumors. The results that the incident of MEN-1 gene mutation for sporadic endocrine tumors was very low suggest that there was different mechanism for tumorigenesis from familial ecdocrine tumors. As far as MEN-1 gene is not responsible gene for sporadic endocrine tumors, it is impossible to produce endocrine tumors by using gene induction technique.2. Genetic analyses of ret-oncogene for familial medullary thyroid carcinoma (FMTC)I studied two families of FMTC and one family of MEN-IIA. Family A , involving three patients with medullary thyroid carcinoma (MTC) and two carriers, was diagnosed FMTC with a RET codon 609 mutation. MTCs in this family were very slow progressive. Clinical strategy of this family is to perform total thyroidectomy for the patient developed MTC. Family B, involving two patients with MTC and two carriers, also was diagnosed FMTC with a RET codon 620 mutation. Family C, involving five patients with MTC, one patient with pheochromocytoma and two carriers, was diagnosed MEN-IIA with a RET codon 634 mutation. I am going to study further these three family members according to the guideline from Japanese Ministry of Health, Labor and Welfare.