Featured Research

from universities, journals, and other organizations

30-year puzzle in breast cancer solved

Date:
May 2, 2014
Source:
Fred Hutchinson Cancer Research Center
Summary:
Mice lacking one copy of a gene called CTCF have abnormal DNA methylation and are markedly predisposed to cancer, new research demonstrates. CTCF is a very well-studied DNA binding protein that exerts a major influence on the architecture of the human genome, but had not been previously linked to cancer. Over 30 years ago, frequent loss of one copy of chromosome 16 was first reported in breast cancer but the gene or genes responsible remained to be identified. This new research answers that 30-year long puzzle.

Dr. Christopher Kemp of Fred Hutch's Human Biology Division.
Credit: Bo Jungmayer / Fred Hutch file

In a new study published today in Cell Reports, scientists at the Fred Hutchinson Cancer Research Center demonstrate that mice lacking one copy of a gene called CTCF have abnormal DNA methylation and are markedly predisposed to cancer.

Related Articles


CTCF is a very well-studied DNA binding protein that exerts a major influence on the architecture of the human genome, but had not been previously linked to cancer. Over 30 years ago, frequent loss of one copy of chromosome 16 was first reported in breast cancer but the gene or genes responsible remained to be identified. Dr. Gala Filippova, staff scientist at Fred Hutch and co-author of the study, originally cloned the human CTCF gene and mapped it to chromosome 16, within the same region that is frequently lost in human cancers. That same year, Dr. Chris Kemp of the Human Biology Division at Fred Hutch, co-authored a paper demonstrating that, in contrast to the predominant "two hit" theory on tumor suppressor genes, it was not necessary to lose both copies, one hit was enough. However, CTCF was ruled out as a candidate breast cancer gene on chromosome 16 simply because it did not conform to the "two hit" model.

"In this current study we explored whether loss of just one copy of the CTCF gene could trigger epigenetic changes and predispose to tumor development," said Dr. Filippova of Fred Hutch. The study demonstrates that indeed, loss of one copy of CTCF caused large scale epigenetic changes and greatly enhanced tumor formation in multiple tissues. In addition, recent large scale analysis of the human cancer genome revealed that deletions or mutations in CTCF are one of the most common events in breast, endometrial, and other human cancers.

Collectively, these findings indicate that CTCF is major tumor suppressor gene in human cancer and highlights the power of the mouse models to prove that a candidate gene has a function in cancer. These results have implications for understanding the origin of DNA methylation alterations in cancer and suggest that epigenetic instability may both precede and accelerate the emergence of cancer.

"This answers a 30 year riddle in cancer research," said Dr. Kemp. "And it shows once again, as we first showed in 1998, that one hit is enough."


Story Source:

The above story is based on materials provided by Fred Hutchinson Cancer Research Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Christopher J. Kemp, James M. Moore, Russell Moser, Brady Bernard, Matt Teater, Leslie E. Smith, Natalia A. Rabaia, Kay E. Gurley, Justin Guinney, Stephanie E. Busch, Rita Shaknovich, Victor V. Lobanenkov, Denny Liggitt, Ilya Shmulevich, Ari Melnick, Galina N. Filippova. CTCF Haploinsufficiency Destabilizes DNA Methylation and Predisposes to Cancer. Cell Reports, 2014; DOI: 10.1016/j.celrep.2014.04.004

Cite This Page:

Fred Hutchinson Cancer Research Center. "30-year puzzle in breast cancer solved." ScienceDaily. ScienceDaily, 2 May 2014. <www.sciencedaily.com/releases/2014/05/140502102512.htm>.
Fred Hutchinson Cancer Research Center. (2014, May 2). 30-year puzzle in breast cancer solved. ScienceDaily. Retrieved November 28, 2014 from www.sciencedaily.com/releases/2014/05/140502102512.htm
Fred Hutchinson Cancer Research Center. "30-year puzzle in breast cancer solved." ScienceDaily. www.sciencedaily.com/releases/2014/05/140502102512.htm (accessed November 28, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, November 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Leaves Orphans Alone in Sierra Leone

Ebola Leaves Orphans Alone in Sierra Leone

AFP (Nov. 27, 2014) — The Ebola epidemic sweeping Sierra Leone is having a profound effect on the country's children, many of whom have been left without any family members to support them. Duration: 01:02 Video provided by AFP
Powered by NewsLook.com
Experimental Ebola Vaccine Shows Promise In Human Trial

Experimental Ebola Vaccine Shows Promise In Human Trial

Newsy (Nov. 27, 2014) — A recent test of a prototype Ebola vaccine generated an immune response to the disease in subjects. Video provided by Newsy
Powered by NewsLook.com
Pet Dogs to Be Used in Anti-Ageing Trial

Pet Dogs to Be Used in Anti-Ageing Trial

Reuters - Innovations Video Online (Nov. 26, 2014) — Researchers in the United States are preparing to discover whether a drug commonly used in human organ transplants can extend the lifespan and health quality of pet dogs. Video provided by Reuters
Powered by NewsLook.com
Today's Prostheses Are More Capable Than Ever

Today's Prostheses Are More Capable Than Ever

Newsy (Nov. 26, 2014) — Advances in prosthetics are making replacement body parts stronger and more lifelike than they’ve ever been. Video provided by Newsy
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:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

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