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
First time-lapse footage of cell activity during limb regeneration
25.10.2016 | eLife
Phenotype at the push of a button
25.10.2016 | Institut für Pflanzenbiochemie
Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.
This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...
Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion
Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
25.10.2016 | Earth Sciences
25.10.2016 | Power and Electrical Engineering
25.10.2016 | Process Engineering