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

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

Im Focus: Penn engineers develop ultrathin, ultralight 'nanocardboard'

When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure

Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...

Im Focus: Coping with errors in the quantum age

Physicists at ETH Zurich demonstrate how errors that occur during the manipulation of quantum system can be monitored and corrected on the fly

The field of quantum computation has seen tremendous progress in recent years. Bit by bit, quantum devices start to challenge conventional computers, at least...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

European Space Talks: Weltraumschrott – eine Gefahr für die Gesellschaft?

23.10.2018 | Event News

 
Latest News

Epoxy compound gets a graphene bump

14.11.2018 | Materials Sciences

Microgel powder fights infection and helps wounds heal

14.11.2018 | Health and Medicine

How algae and carbon fibers could sustainably reduce the athmospheric carbon dioxide concentration

14.11.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>