Thyroid has unexpectedly high mutation rate
German scientists have found that there is a strikingly high spontaneous mutation rate (SMR) in the thyroid gland.
Reporting in the journal Endocrinology, the team explains that thyroid nodules are commonly found among more than 50% of the general population, and are predominantly characterized by somatic genetic changes.
However, the high frequency of neoplasms in thyroid tissue cannot be explained by a high proliferation rate as in tumor-prone tissues such as the colon and breast, the investigators note.
Seeking a possible explanation for this discrepancy, Knut Krohn, from the University of Leipzig, and co-workers examined thyroid SMR in an in vivo transgenic mouse model, and a comet assay to determine thyroid DNA damage in rats.
Findings revealed that the SMR in the thyroid tissues of the mice ranged from 56 x 10-5 to 72 x 10-5 mutants per wild-type sequence, about eight to 10 times higher than the rate found in the liver tissues of the animals, characterized at 6.7 x 10-5.
Results of single cell comet assay, used to assess DNA damage in the thyroid, liver, and lungs of young rats, showed that there were two- to three-fold increased levels of oxidized pyrimidine and two- to four-fold increased purine levels in the thyroid compared with liver and lung tissues.
Finally, assessing the distribution of thyrotropin releasing hormone receptor (TSHR) mutations in humans using the TSHR database, Krohn et al detected 184 individuals with hyperfunctioning thyroid adenoma, adenomatous nodules or carcinomas with somatic mutations of the human TSHR.
Among these people, there was an unexpectedly high frequency of C->T transitions, at more than 32%, about four times the statistical average.
"Interpretation of our data suggests that the strikingly high SMR in thyroid could be due to oxidative DNA damage caused by the specifics of thyroid hormone synthesis which involves generation of free radicals and reactive oxygen," the researchers state.
"A high frequency of somatic mutations already in the normal thyroid will prompt us to study mutagenesis in the thyroid challenged either by nutritional restriction (eg, iodine deficiency), genetic defects (eg, oncogene expression) or radiation," they add.