Most cancer cells exhibit gross chromosomal aberrations, for instance, gains or losses of whole chromosomes or parts of chromosomes.
This striking feature of many cancers is called aneuploidy and is often accompanied by chromosomal instability (CIN), an increased rate of gain and loss of chromosomes or chromosome fractions. Aneuploidy in cancer cells was first observed 100 years ago by the German biologist Theodor Bovery.
To this day, scientists do not fully understand how cancer cells can cope with such a seemingly chaotic disposition, sometimes even enhancing their proliferation potential.
Increased levels of CIN worsens the prognosis in Estrogen-receptor-positive (or ER+) breast cancer, which comprises about 75% of all breast cancers. This conundrum motivated two teams lead by the Biomathematician Maik Kschischo (University of Applied Sciences Koblenz, Germany) and the Oncologist Charles Swanton (Cancer Research UK, London) to ask, how CIN modulates the activity of other genes and what the phenotypic consequences are.
The scientists designed a computational workflow to filter out core regulator genes whose DNA copy number in high CIN tumours affects the RNA expression of many other genes. Intriguingly, for two of these core regulator genes, TPX2 and UBE2C, they found their DNA copy number to be highly correlated with gene expression biomarkers used for forecasting clinical outcome and response to chemotherapy. In addition, these genes were also associated with markers for cellular proliferation.
These results shed a new light on two open questions: In recent years, various gene expression signatures were approved and marketed to predict the clinical outcome and the response to chemotherapy for woman suffering from ER+ breast cancer.
These signatures help doctors to decide on the optimal treatment strategies for individual patients. What puzzled scientists was, that these signatures have so few genes in common and that no obvious biological process or function could be identified which explains the prognostic power of these signatures. The teams of Kschischo and Swanton show, that a good part of the signal in these signatures is related to CIN and the CIN core regulators UBE2C and TPX2.
Secondly, these results support the view that CIN and aneuploidy are not just byproducts of the cancerous state, but are essential for the evolutionary processes involved in cancer development. By means of natural selection, cancer cells acquire DNA copy aberrations of core regulator genes which enable adaptation to CIN and aneuploidy and also modulation of their proliferative potential.
We still have no consistent picture about the evolutionary forces involved in cancer development and progression. However, recent progress reported here and by others and future work combining computational analysis of larger and larger data sets with targeted experimentation will help to better understand what really drives cancer.
Innovative therapeutic and diagnostic approaches will greatly profit from taking the heterogeneity and adaptability of cancer cells promoted by CIN and aneuploidy into account.
Chromosomal instability selects gene copy number variants encoding core regulators of proliferation in ER+ breast cancer.
Cancer Res 2014 Jun 26. Epub 2014 Jun 26.
David Endesfelder, Rebecca A. Burrell, Nnennaya Kanu, Nicholas McGranahan, Mike Howell, Peter J Parker, Julian Downward, Charles Swanton, Maik Kschischo
Melanie Dargel-Feils | idw - Informationsdienst Wissenschaft
New Model of T Cell Activation
27.05.2016 | Albert-Ludwigs-Universität Freiburg im Breisgau
Fungi – a promising source of chemical diversity
27.05.2016 | Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie - Hans-Knöll-Institut (HKI)
A biological and energy-efficient process, developed and patented by the University of Innsbruck, converts nitrogen compounds in wastewater treatment facilities into harmless atmospheric nitrogen gas. This innovative technology is now being refined and marketed jointly with the United States’ DC Water and Sewer Authority (DC Water). The largest DEMON®-system in a wastewater treatment plant is currently being built in Washington, DC.
The DEMON®-system was developed and patented by the University of Innsbruck 11 years ago. Today this successful technology has been implemented in about 70...
Permanent magnets are very important for technologies of the future like electromobility and renewable energy, and rare earth elements (REE) are necessary for their manufacture. The Fraunhofer Institute for Mechanics of Materials IWM in Freiburg, Germany, has now succeeded in identifying promising approaches and materials for new permanent magnets through use of an in-house simulation process based on high-throughput screening (HTS). The team was able to improve magnetic properties this way and at the same time replaced REE with elements that are less expensive and readily available. The results were published in the online technical journal “Scientific Reports”.
The starting point for IWM researchers Wolfgang Körner, Georg Krugel, and Christian Elsässer was a neodymium-iron-nitrogen compound based on a type of...
In the Beyond EUV project, the Fraunhofer Institutes for Laser Technology ILT in Aachen and for Applied Optics and Precision Engineering IOF in Jena are developing key technologies for the manufacture of a new generation of microchips using EUV radiation at a wavelength of 6.7 nm. The resulting structures are barely thicker than single atoms, and they make it possible to produce extremely integrated circuits for such items as wearables or mind-controlled prosthetic limbs.
In 1965 Gordon Moore formulated the law that came to be named after him, which states that the complexity of integrated circuits doubles every one to two...
Characterization of high-quality material reveals important details relevant to next generation nanoelectronic devices
Quantum mechanics is the field of physics governing the behavior of things on atomic scales, where things work very differently from our everyday world.
When current comes in discrete packages: Viennese scientists unravel the quantum properties of the carbon material graphene
In 2010 the Nobel Prize in physics was awarded for the discovery of the exceptional material graphene, which consists of a single layer of carbon atoms...
24.05.2016 | Event News
20.05.2016 | Event News
19.05.2016 | Event News
27.05.2016 | Awards Funding
27.05.2016 | Life Sciences
27.05.2016 | Life Sciences