Featured Research

from universities, journals, and other organizations

Mutations in cancer often affect the X chromosome

Date:
October 18, 2013
Source:
German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)
Summary:
Every cell in a woman's body inactivates one of its two X chromosomes. Scientists have discovered that various types of cancer exhibit an abnormally huge numbers of mutations in the inactive X chromosome. The findings help scientists understand how mutations accumulate in damaged cells and eventually lead to the development of cancer.

Every case of cancer originates from changes in a person's genetic material (mutations). These usually occur as "somatic mutations" in individual cells during an individual's lifetime, rather than being inherited from a person's parents. "Over time, the original damaged cell accumulates additional mutations, and it is still largely unknown why," says Prof. Roland Eils, who leads bioinformatics departments both at DKFZ and Heidelberg University.

By studying when and where mutations occur the researchers hope to gain insights into the early mechanisms that send cells along a pathway to cancer. The new international study coordinated by Roland Eils has now for the first time analyzed the exact distribution of somatic mutations in the genomes of tumor cells of various types of cancer. Mutations do not affect all regions of the genome to the same extent. It is known, for example, that the number of somatic mutations depends on the sequence of bases making up a gene and the frequency at which it is transcribed into RNA molecules.

In the current study, the researchers analyzed the genome sequences of more than 400 tumors from patients suffering from twelve different types of cancer, including brain cancer in children and adults, leukemias and breast cancer.

The scientists were surprised to find that mutations were extremely frequent in the X chromosome of females, which is responsible for determining sex. In many cancers, this chromosome displayed from two to four times as many mutations as were observed in the other chromosomes. Every cell in a female has two copies of the X chromosome and interestingly the rate was not the same in the two copies. From embryonic development onwards, one of the copies is inactivated in each cell. The higher mutation rate exclusively affects the inactive copy.

This phenomenon was not found in male cancer patients, whose cells carry only one X chromosome, or in inactive X chromosomes of healthy female cells. And in rapidly growing tumors, mutations were found to be particularly frequent in the inactive X chromosome. The researchers also discovered that the build-up of mutations occurs at a very early stage of carcinogenesis.

Prior to each cell division, the DNA in the original cell is duplicated. The inactive X chromosome is always the last to be duplicated. "Our theory is that cells which have accidentally undergone a growth-promoting mutation experience a state of stress caused by the rapid cell division," says Natalie Jäger, first author of the article. "They may not have enough time to repair errors, or they may lack enough of the building blocks necessary to create DNA. These problems mainly affect genomic regions that are duplicated at a late stage such as the inactive X chromosome."

Roland Eils adds: "This finding helps us understand how cellular stress accelerates the fatal process of carcinogenesis and thus contributes to an accumulation of ever more mutations in a cancer cell."


Story Source:

The above story is based on materials provided by German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ). Note: Materials may be edited for content and length.


Journal Reference:

  1. Natalie Jäger, Matthias Schlesner, David T.W. Jones, Simon Raffel, Jan-Philipp Mallm, Kristin M. Junge, Dieter Weichenhan, Tobias Bauer, Naveed Ishaque, Marcel Kool, Paul A. Northcott, Andrey Korshunov, Ruben M. Drews, Jan Koster, Rogier Versteeg, Julia Richter, Michael Hummel, Stephen C. Mack, Michael D. Taylor, Hendrik Witt, Benedict Swartman, Dietrich Schulte-Bockholt, Marc Sultan, Marie-Laure Yaspo, Hans Lehrach, Barbara Hutter, Benedikt Brors, Stephan Wolf, Christoph Plass, Reiner Siebert, Andreas Trumpp, Karsten Rippe, Irina Lehmann, Peter Lichter, Stefan M. Pfister, Roland Eils. Hypermutation of the Inactive X Chromosome Is a Frequent Event in Cancer. Cell, 2013; DOI: 10.1016/j.cell.2013.09.042

Cite This Page:

German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ). "Mutations in cancer often affect the X chromosome." ScienceDaily. ScienceDaily, 18 October 2013. <www.sciencedaily.com/releases/2013/10/131018132203.htm>.
German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ). (2013, October 18). Mutations in cancer often affect the X chromosome. ScienceDaily. Retrieved July 29, 2014 from www.sciencedaily.com/releases/2013/10/131018132203.htm
German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ). "Mutations in cancer often affect the X chromosome." ScienceDaily. www.sciencedaily.com/releases/2013/10/131018132203.htm (accessed July 29, 2014).

Share This




More Plants & Animals News

Tuesday, July 29, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deadly Ebola Virus Threatens West Africa

Deadly Ebola Virus Threatens West Africa

AP (July 28, 2014) — West African nations and international health organizations are working to contain the largest Ebola outbreak in history. It's one of the deadliest diseases known to man, but the CDC says it's unlikely to spread in the U.S. (July 28) Video provided by AP
Powered by NewsLook.com
Traditional African Dishes Teach Healthy Eating

Traditional African Dishes Teach Healthy Eating

AP (July 28, 2014) — Classes are being offered nationwide to encourage African Americans to learn about cooking fresh foods based on traditional African cuisine. The program is trying to combat obesity, heart disease and other ailments often linked to diet. (July 28) Video provided by AP
Powered by NewsLook.com
Asteroid's Timing Was 'Colossal Bad Luck' For The Dinosaurs

Asteroid's Timing Was 'Colossal Bad Luck' For The Dinosaurs

Newsy (July 28, 2014) — The asteroid that killed the dinosaurs struck at the worst time for them. A new study says that if it hit earlier or later, they might've survived. Video provided by Newsy
Powered by NewsLook.com
Raw: Sea Turtle Hatchlings Emerge from Nest

Raw: Sea Turtle Hatchlings Emerge from Nest

AP (July 27, 2014) — A live-streaming webcam catches loggerhead sea turtle hatchlings emerging from a nest in the Florida Keys. (July 27) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins