A significant number of autumnous adenomas carry a mutation in a gene that is involved in controlling cell proliferation and differentiation. EZH1 – or Enhancer of Zeste Homolog 1 – is the scientific name of this gene. ( Graphic: Davice Calebiro / Kerstin Bathon)
Autonomous adenomas are the most common benign tumors of the thyroid gland. Mutations in 2 genes account for around 70% of the cases. Scientists have now discovered another key trigger. Thyroid hormones are involved in controlling many functions of the human body: They influence sugar, lipid and protein metabolism, regulate body temperature, heart rate, circulation and many more functions. In children, they also control the development of the brain and nerves as well as bone growth. Hyperthyroidism symptoms include persistent restlessness, irritability, insomnia, inexplicable weight loss, excessive sweating and an increased pulse. Untreated hyperthyroidism has severe consequences, including, most importantly, a higher mortality for cardiovascular disease.
In many cases, such a hyperfunction is triggered by thyroid tumours, most of which are benign. Among them, autonomous adenoma accounts for the majority. “We know that special mutations in certain genes are responsible for around 70% of all autonomous adenomas,” says Dr. Davide Calebiro.
However, it has been unknown until recently whether these mutations alone are sufficient to prompt thyroid cells to proliferate and produce excessive hormones, or whether additional factors have to be present. Also, it was unclear which factors are involved in the genesis of the remaining 30% of autonomous adenomas.
“For our study, we examined 19 autonomous adenomas using whole exome sequencing,” Calebiro describes their approach. This technique does not investigate the entire genome of the cells; rather the focus is on the so-called exons of the genes – which are the pieces that are actually translated into proteins. Usually, the exons (“exome”) account for 1-2% of the total DNA. “We were able to show that a significant number of these adenomas carry a mutation in a gene that is involved in controlling cell proliferation and differentiation,” Calebiro further explained.
EZH1 – or Enhancer of Zeste Homolog 1 – is the scientific name of this gene. EZH1 mutations work synergistically with the other known mutations, leading to the formation of autonomous adenomas. Moreover, functional studies show that EZH1 mutations modify signal pathways that cause thyroid cells to proliferate.
“We were able to show that a hot-spot mutation in the EZH1 gene is the second most common genetic defect in autonomous adenomas,” Davide Calebiro said. The frequent association of EZH1 mutations with those in previously known genes points to a “two-hit model.” ie the first mutation increases the disposition for the formation of tumours, whereas the second triggers the disease process. https://www.uni-wuerzburg.de/en/sonstiges/meldungen/detail/artikel/zwei-treffer-machen-den-schilddruesentumor/
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