Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Thyroid tumour: it takes two to tango

09.08.2016

Autonomous adenomas are the most common benign tumours of the thyroid gland. Mutations in two genes account for around 70 percent of the cases. Scientists from the University of Würzburg 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.


A significant number of autumnous adenomas carry a mutation in a gene that is involved in controlling cell proliferation and differentiation. EZH1 is its scientific name.

Graphic: Davice Calebiro / Kerstin Bathon

No wonder that hyperthyroidism has several detrimental effects in the affected patients. Typical 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.

Search for the responsible mutations

In many cases, such a hyperfunction is triggered by thyroid tumours, most of which are benign. Among them, the so-called autonomous adenoma accounts for the majority. Its genesis is in general well understood: "We know that special mutations in certain genes are responsible for around 70 percent of all autonomous adenomas," says Dr. Davide Calebiro from the Institute of Pharmacology and Toxicology and the Bio-Imaging Center of the University of Würzburg.

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 percent of autonomous adenomas.

Publication in the Journal of Clinical Investigation

In the search for other causes of the disease, an international team of researchers, led by Davide Calebiro, Luca Persani from the University of Milan and Ralf Paschke from the University of Calgary, have now scored a success. Their results have been published in the current issue of Journal of Clinical Investigation (JCI) – Davide Calebiro is the first author of the study. Researchers from the group of Professor Martin Fassnacht from the Würzburg University Hospital also participated in the study. The Interdisciplinary Center for Clinical Research (IZKF) of the University of Würzburg supported the work.

"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.

Gene mutation causes increased cell proliferation

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 puts the result of their recently published work in a nutshell. In his opinion, the frequent association of EZH1 mutations with those in previously known genes points to a "two-hit model". Accordingly, the first mutation increases the disposition for the formation of tumours, whereas the second triggers the disease process.

Recurrent EZH1 mutations are a second hit in autonomous thyroid adenomas. Davide Calebiro, Elisa S. Grassi, Markus Eszlinger, Cristina L. Ronchi, Amod Godbole, Kerstin Bathon, Fabiana Guizzardi, Tiziana de Filippis, Knut Krohn, Holger Jaeschke, Thomas Schwarzmayr, Rifat Bircan, Hulya Iliksu Gozu, Seda Sancak, Marek Niedziela, Tim M. Strom, Martin Fassnacht, Luca Persani, Ralf Paschke. Journal of Clinical Investigation, online published 08.08.16. doi:10.1172/JCI84894

Contact

PD Dr. Davide Calebiro, Phone: +49 931 31-80067, E-mail: davide.calebiro@toxi.uni-wuerzburg.de

Gunnar Bartsch | Julius-Maximilians-Universität Würzburg

More articles from Life Sciences:

nachricht Single-stranded DNA and RNA origami go live
15.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard

nachricht New antbird species discovered in Peru by LSU ornithologists
15.12.2017 | Louisiana State University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First-of-its-kind chemical oscillator offers new level of molecular control

DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.

Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Engineers program tiny robots to move, think like insects

15.12.2017 | Power and Electrical Engineering

One in 5 materials chemistry papers may be wrong, study suggests

15.12.2017 | Materials Sciences

New antbird species discovered in Peru by LSU ornithologists

15.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>