Analysis of mitochondrial DNA mutations in D-loop region in thyroid lesions.
BACKGROUND
Mitochondrial defects have been associated with various human conditions including cancers.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Our results indicate that mtDNA alterations in the D-loop region could happen before tumorigenesis in thyroid, and they might also accumulate during tumorigenesis.
Ding
Zhinan
Z
Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical College, Wenzhou 325035, China.
Ji
Jingzhang
J
Chen
Guorong
G
Fang
Hezhi
H
Yan
Shihui
S
Shen
Lijun
L
Wei
Jia
J
Yang
Kaiyan
K
Lu
Jianxin
J
Bai
Yidong
Y
D000236:Adenoma / Q000235:genetics / Q000473:pathology; D017931:DNA Primers; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics*; D018450:Disease Progression; D005784:Gene Amplification; D006042:Goiter / Q000235:genetics* / Q000473:pathology; D006044:Goiter, Nodular / Q000235:genetics / Q000473:pathology; D006801:Humans; D053842:Microsatellite Instability; D009154:Mutation; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012016:Reference Values; D013959:Thyroid Diseases / Q000235:genetics* / Q000473:pathology; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
D017931:DNA Primers; D004272:DNA, Mitochondrial