甲状腺乳头状癌细胞线粒体DNAD环区的突变

Somatic mutations of mitochondrial DNA in thyroid papillary carcinoma

目的研究线粒体 DNA D 环(D-loop)区在甲状腺乳头状癌中的突变情况。方法对35例甲状腺乳头状癌患者的癌组织和外周血淋巴细胞抽提线粒体 DNA,再行 PCR 产物直接测序的方法对线粒体 D 环区的两个高变区(HVR-Ⅰ和 HVR-Ⅱ)进行突变检测。结果在35例甲状腺乳头状癌患者中有2例发现突变,突变率为5.7%。突变位点5个,都在 HVR-Ⅱ区,均为同质性突变,其中2个属于微卫星不稳定,其余3个属于碱基替代突变。研究同时发现2个尚未报道的新的多态位点(nt324:C→G,ntl6092:T→A)。结论与其他上皮来源肿瘤相比,线粒体 DNA D 环区在甲状腺乳头状癌中的突变率不高,其与甲状腺乳头状癌发生的关系仍有待于进一步研究。

Objective To analyze the somatic mutations in the D-loop of mtDNA and further evaluate the possibility of mitochondrial genetic instability in thyroid papillary carcinoma. Methods Hypervariable regions （ HVR- I and HVR- Ⅱ ） in the D-loop of mtDNA from the specimen of 35 thyroid papillary cancers and matched lymphocytes were amplified by PCR, and then were sequenced. Results Comparing the sequences of tumors to those of matched lymphocytes and normal thyroid tissues, 5 somatic mutations in 2 patients （5.7%） were found. Two mutations were insertions of C in a poly-cytidine （ nt303 ） microsatellite, and 3 at positions 73, 152 and 194 in HVR-Ⅱ. In addition, of the 294 genetic variants detected, 292 were previously recorded polymorphisms, whereas 2 were new polymorphisms （nt324：C→G, nt16092 ：T→A）. Conclusions Mutations in the D-loop of mtDNA were found in thyroid papillary cancers, this mutation rate was lower than the reported rate of alteration in tumors of epithelial origin, and further work is required to elucidate the relationship between this mutations and the development of thyroid papillary carcinoma.