Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Kidney tumor: Genetic trigger discovered


Scientists at the University of Würzburg have identified new molecular biomarkers for rare kidney tumors in small children. These may be targets for new therapies.

It is malignant and can occur in the first months of infants' lives or even before birth: congenital mesoblastic nephroma (CMN). Fortunately, the kidney tumor is very rare and can often be cured with surgery. However, there are no other specific treatment options - also because of the as yet unclarified causes of this tumor.

Classical mesoblastic nephroma with typical bundles of spindle cells showing a strong nuclear positivity for pERK.

Photo: Andreas Rosenwald

An enzyme becomes hyperactive

Three subtypes of this kidney tumor are known. An international team of researchers has now identified a genetic driver for one of these subtypes. Jenny Wegert and Professor Manfred Gessler from the Department of Developmental Biochemistry at the Biozentrum of Julius-Maximilians-University Würzburg (JMU) were responsible for this breakthrough, together with Sam Behjati and Grace Collord from the Wellcome Sanger Centre (Cambridge) and Christian Vokuhl from the University of Kiel. The results of their work are published in the current issue of the journal Nature Communications.

"Three subgroups can be defined in congenital mesoblastic nephroma in tissue sections: classical, cellular and mixed nephromas," explains Manfred Gessler. A characteristic change in the chromosomes has long been known to trigger cellular CMN. In this case, two genes fuse with each other, which leads to the overshooting activity of an enzyme. No typical genetic alterations were known for the classical variant of CMN, however.

Novel mutation detected

This has now changed: "By genome analysis of tumor and blood samples from patients, we were able to detect a novel mutation of the receptor for the epidermal growth factor, EGFR, in over 70 percent of classical CMN," Wegert describes the central result of the study. The scientists discovered a doubling of the enzymatically active kinase region in the genome of the affected cells. As a result, the EGF receptor becomes overactive and the tumor cells are permanently stimulated to grow. Further investigations have shown that in the majority of cases the mixed variant of the tumor also has such an EGFR mutation.

In both the classical and cellular variants of CMN, the genetic alterations trigger one of the most important signalling pathways for the activation of cell growth: the so-called MAP kinase cascade. Among other things, they switch on the BRAF kinase present in the cell. "Interestingly, the gene for this protein was also mutated in some of the tumors in which neither the mutation responsible for the classical nor the cellular variant could be detected," explained Gessler.

In these cases, the affected gene lost a region responsible for inhibiting BRAF kinase activity, with the result that the protein is permanently active and the MAP kinase cascade remains switched on.

Parallels to tumors in adults

The research team has thus succeeded in almost all cases in attributing this rare tumor of infancy to the activation of a central signalling pathway, which also plays an important role in many adult tumors, which Professor Andreas Rosenwald from the Institute of Pathology at the JMU was able to substantiate with corresponding staining of tumor section.

Especially for CMN patients who cannot be adequately treated surgically, these findings may now provide new treatment approaches by transferring proven principles of adult oncology to the therapy of congenital mesoblastic nephroma therapy.

Recurrent intragenic rearrangements of EGFR and BRAF in soft tissue tumors of infants. Nature Communications, doi: 10.1038/s41467-018-04650-6, .

University of Wuerzburg

Home to just under 29,000 students, Julius-Maximilians-Universität Würzburg (JMU) is one of the largest universities in Germany. True to its motto ‘Science for Society’, JMU is committed to advancing research in fields that are relevant for the future, focussing on eight pillars: Life Sciences / Health Sciences / Molecular Chemistry and Materials / Quantum Phenomena in New Materials / Digital Society / Cultural Heritage / Norms and Behavior / Global Changes.

The Wellcome Sanger Institute

The Wellcome Sanger Institute is one of the world's leading genome centres. Through its ability to conduct research at scale, it is able to engage in bold and long-term exploratory projects that are designed to influence and empower medical science globally. Institute research findings, generated through its own research programmes and through its leading role in international consortia, are being used to develop new diagnostics and treatments for human disease. To celebrate its 25th year in 2018, the Institute is sequencing 25 new genomes of species in the UK.


Prof. Dr. Manfred Gessler, Chair of Developmental Biochemistry,
T: +49 931 31 84159 / 84160 (Secr.),

Gunnar Bartsch | Julius-Maximilians-Universität Würzburg
Further information:

More articles from Life Sciences:

nachricht AI-driven single blood cell classification: New method to support physicians in leukemia diagnostics
13.11.2019 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Small RNAs link immune system and brain cells
13.11.2019 | Goethe-Universität Frankfurt am Main

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Magnets for the second dimension

If you've ever tried to put several really strong, small cube magnets right next to each other on a magnetic board, you'll know that you just can't do it. What happens is that the magnets always arrange themselves in a column sticking out vertically from the magnetic board. Moreover, it's almost impossible to join several rows of these magnets together to form a flat surface. That's because magnets are dipolar. Equal poles repel each other, with the north pole of one magnet always attaching itself to the south pole of another and vice versa. This explains why they form a column with all the magnets aligned the same way.

Now, scientists at ETH Zurich have managed to create magnetic building blocks in the shape of cubes that - for the first time ever - can be joined together to...

Im Focus: A new quantum data classification protocol brings us nearer to a future 'quantum internet'

The algorithm represents a first step in the automated learning of quantum information networks

Quantum-based communication and computation technologies promise unprecedented applications, such as unconditionally secure communications, ultra-precise...

Im Focus: Distorted Atoms

In two experiments performed at the free-electron laser FLASH in Hamburg a cooperation led by physicists from the Heidelberg Max Planck Institute for Nuclear physics (MPIK) demonstrated strongly-driven nonlinear interaction of ultrashort extreme-ultraviolet (XUV) laser pulses with atoms and ions. The powerful excitation of an electron pair in helium was found to compete with the ultrafast decay, which temporarily may even lead to population inversion. Resonant transitions in doubly charged neon ions were shifted in energy, and observed by XUV-XUV pump-probe transient absorption spectroscopy.

An international team led by physicists from the MPIK reports on new results for efficient two-electron excitations in helium driven by strong and ultrashort...

Im Focus: A Memory Effect at Single-Atom Level

An international research group has observed new quantum properties on an artificial giant atom and has now published its results in the high-ranking journal Nature Physics. The quantum system under investigation apparently has a memory - a new finding that could be used to build a quantum computer.

The research group, consisting of German, Swedish and Indian scientists, has investigated an artificial quantum system and found new properties.

Im Focus: Shedding new light on the charging of lithium-ion batteries

Exposing cathodes to light decreases charge time by a factor of two in lithium-ion batteries.

Researchers at the U.S. Department of Energy's (DOE) Argonne National Laboratory have reported a new mechanism to speed up the charging of lithium-ion...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

High entropy alloys for hot turbines and tireless metal-forming presses

05.11.2019 | Event News

Smart lasers open up new applications and are the “tool of choice” in digitalization

30.10.2019 | Event News

International Symposium on Functional Materials for Electrolysis, Fuel Cells and Metal-Air Batteries

02.10.2019 | Event News

Latest News

Magnets for the second dimension

12.11.2019 | Machine Engineering

New efficiency world record for organic solar modules

12.11.2019 | Power and Electrical Engineering

Non-volatile control of magnetic anisotropy through change of electric polarization

12.11.2019 | Physics and Astronomy

Science & Research
Overview of more VideoLinks >>>