Analysis of mitochondrial DNA mutations in D-loop region in thyroid lesions

• Published in: Biochimica et biophysica acta Vol. 1800; no. 3; pp. 271 - 274
• Main Authors: Ding, Zhinan, Ji, Jingzhang, Chen, Guorong, Fang, Hezhi, Yan, Shihui, Shen, Lijun, Wei, Jia, Yang, Kaiyan, Lu, Jianxin, Bai, Yidong
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2010
• Subjects: Adenoma - genetics; Adenoma - pathology; D-loop region; Disease Progression; DNA Primers; DNA, Mitochondrial - chemistry; DNA, Mitochondrial - genetics; Gene Amplification; Goiter - genetics; Goiter - pathology; Goiter, Nodular - genetics; Goiter, Nodular - pathology; Humans; Microsatellite Instability; Mitochondrial DNA mutation; Mitochondrial microsatellite instability; Mutation; Point Mutation; Polymerase Chain Reaction; Reference Values; Thyroid; Thyroid Diseases - genetics; Thyroid Diseases - pathology; Thyroid Neoplasms - genetics; Thyroid Neoplasms - pathology; Tumor progression; Mitochondrial DNA mutation; Mitochondrial microsatellite instability; D-loop region; Tumor progression; Thyroid
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2009.05.009

Mitochondrial defects have been associated with various human conditions including cancers. We analyzed the mutations at the mitochondrial DNA (mtDNA) in patients with different thyroid lesions. In particular, in order to investigate if the accumulation of mtDNA mutations play a role in tumor progression, we studied the highly variable main control region of mtDNA, the displacement-loop (D-loop) in patients with non-tumor nodular goiters, with benign thyroid adenomas, and with malignant thyroid carcinomas. Total thyroid tumor or goiter samples were obtained from 101 patients, matched with nearby normal tissue and blood from the same subject. Noticeably, mitochondrial microsatellite instability (mtMSI) was detected in 2 of 19 nodular goiters (10.53%), and 8 of 77 (10.39%) malignant thyroid carcinomas. In addition, 6 patients, including 5 (6.49%) with malignant thyroid carcinomas and 1 (5.26%) with nodular goiter, were found to harbor point mutations. The majority of the mutations detected were heteroplasmic. Our results indicate that mtDNA alterations in the D-loop region could happen before tumorigenesis in thyroid, and they might also accumulate during tumorigenesis.