毒性多结节性甲状腺肿细胞的生物学行为改变

Change of biological behavior of toxic multi-nodular goiter cells

目的观察毒性多结节性甲状腺肿（TMG）促甲状腺激素受体（TSHR）基因突变情况及探讨TSHR基因突变引起TMG细胞的生物学行为的改变。方法将21例TMG患者手术切除标本中甲状腺结节组织及其作为对照组的结节周围正常的甲状腺组织分别提取DNA，对目的基因片段进行扩增聚合酶链反应（PCR）反应及DNA测序分析。结果21例TMG标本中发现11例存在TSHR基因突变（52．3％）。其中，4例碱基插入性突变：在1928和1929位核酸之间播入了一个鸟嘌呤（G），使该密码子609位以后的氨基酸发生了移码突变；7例为点突变：第613位密码子的第一碱基即第1937位核苷酸发生T—A转换，使密码子由TAC变为AAC，酪氨酸被天冬酰胺置换即Tyr613Asn（TAC—AAC）。对照组未发现TSHR基因突变。结论基因突变的TSHR对TMG细胞的生物学行为的改变起着一定作用。

Objective To observe thyrotropin receptor （TSHR） mutations of toxic multi-nodular goiter （TMG） and change of biological behavior of TMG cells caused by TSHR mutation. Methods Nodular specimens were obtained from 21 cases diagnosed as TMG,with normal thyroid specimens adjacent to the nodules as control. Genomic DNAs were isolated from thyroid nodules and normal tissues of 21 TMGs. After amplifying the related regions, the precise localization of the mutations was identified by automatic DNA sequence analysis. Results TSHR mutations were identified in 11 （52.3%） of 21 TMGs. Four samples had insertion mutation with a guanosine monophosphate inserted between the nucleotide of 1928 and 1929 ,making the genes after codon 609 frame shift mutation;Seven samples had point mutation in codon 613 with tyrosine replaced by asparagine. Conclusion The TSHR mutations play a certain role in change of biological behavior of TMGs＇ cells.