Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Twoards diciphering chromosomal chaos in (ER+ ) breast cancer

05.08.2014

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.

Reference:
Chromosomal instability selects gene copy number variants encoding core regulators of proliferation in ER+ breast cancer.
Cancer Res.
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

http://cancerres.aacrjournals.org/content/early/2014/06/26/0008-5472.CAN-13-2664...

Melanie Dargel-Feils | idw - Informationsdienst Wissenschaft
Further information:
http://www.hs-koblenz.de

Further reports about: CIN Cancer DNA UBE2C aneuploidy breast chemotherapy chromosomal genes instability proliferation

More articles from Life Sciences:

nachricht Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel

nachricht The Nagoya Protocol Creates Disadvantages for Many Countries when Applied to Microorganisms
05.12.2016 | Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

IHP presents the fastest silicon-based transistor in the world

05.12.2016 | Power and Electrical Engineering

InLight study: insights into chemical processes using light

05.12.2016 | Materials Sciences

High-precision magnetic field sensing

05.12.2016 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>