家族性甲状腺髓样癌的遗传与临床研究

目的:调查一家系中甲状腺髓样癌(MTC)的发病情况与RET原癌基因突变与遗传的关系及临床意义。方法:提取21名家系成员外周血DNA。采用聚合酶链反应(PCR)及直接DNA测序技术,检测RET外显子突变状况,并检测该21名成员的血清降钙素、甲状旁腺素及癌胚抗原水平。结果:21名受检者中所有MTC患者7例及3例非MTC患者,检出RET第11外显子634位的tgc-tac突变。10名突变者中降钙素增高9例,甲状旁腺素增高8例,癌胚抗原增高6例。结论:FMTC具有明显遗传性,RET原癌基因11号外显子634位密码子(cys-tyr)突变是FMTC发病的分子生物学基础,检测RET原癌基因突变,结合血清降钙素,癌胚抗原和B超,有助于家系中高危人群的早期发现,早期治疗。

Genetic and clinical research of familial medullary thyroid carcinoma

OBJECTIVE:To investigate the mutation status of the RET proto-oncogene in an MTC pedigree and to further study the genetic and clinical significance of RET mutation.METHODS:DNA samples were collected from peripheral blood of 21 family members,including 7 MTC patients.PCR amplification and DNA sequencing were performed to detect the mutations of RET exons.Serum calcification,parathyroid hormone and CEA were examined in all these 21 family members.RESULTS:A mutation of TGC to CGC at codon 634 in exon 11 of RET was found in 10 family members,including all 7 MTC patients.Serum calcitonin,parathyroid hormone and CEA levels were elevated in 9,8,and 6 of the 10 mutation carriers,respectively.CONCLUSIONS:FMTC is hereditary.The mutation at codon 634 in exon 11 of RET is the molecular biological basis for the occurrence of FMTC.The combined detection of RET mutation,serum calcitonin and CEA examination,as well as B-ultrasonography,may be helpful to the early diagnosis and early treatment of high risk members of the MTC pedigrees.