Featured Research

from universities, journals, and other organizations

Scientists Discover "Missing Link" Between Rare Disease And Inherited Forms Of Breast Cancer

Date:
February 16, 2001
Source:
Dana-Farber Cancer Institute
Summary:
Scientists following the gene trail of one of the world's rarest diseases have found it leads to an entirely unexpected place - to BRCA1, a gene that, when defective, is the most common source of inherited breast cancer.

Boston - Scientists following the gene trail of one of the world's rarest diseases have found it leads to an entirely unexpected place - to BRCA1, a gene that, when defective, is the most common source of inherited breast cancer.

In two studies published in the February issue of Molecular Cell, researchers led by Alan D'Andrea, M.D., of Dana-Farber Cancer Institute show how genes involved in a condition called Fanconi anemia form a "pathway" to the activation of BRCA1. If BRCA1 or any of the Fanconi genes are abnormal, the risk of cancer increases dramatically.

"There's strong evidence that under normal conditions, BRCA1 helps repair DNA damage in cells, preventing the cells from becoming cancerous," D'Andrea says. "But until now, little was known of how BRCA1 is switched on. This new study presents a pathway leading to BRCA1 activation - and it was discovered by studying a condition that's known to affect only 500 families in the United States."

The finding means that physicians may soon have a new tool for determining who is at risk for inherited breast cancer. Since a mutation in any of the Fanconi genes can block BRCA1 from being activated - thereby preventing it from doing its DNA repair work - testing for those mutations may offer a way of identifying women likely to develop breast tumors.

Although inherited forms of breast cancer comprise only about 5 percent of all breast cancer cases, testing for mutations in Fanconi genes could help identify women with normal BRCA1 genes who are still at risk for the disease.

The new study is an outgrowth of D'Andrea's research into Fanconi anemia, an inherited disorder that causes children to develop bone marrow failure by age five, leaving them unable to produce oxygen-carrying red blood cells. While a bone marrow transplant can cure the failure, many patients go on to develop cancer as young adults - usually leukemia, but also tumors of the brain, head and neck, esophagus, or other organs.

The disease is caused by a mutation in any of seven genes within human cells. In previous research, D'Andrea and his colleagues showed that proteins produced from five of those genes form an enzyme that activates a sixth gene. In their first paper in this week's Molecular Cell, research teams led by D'Andrea and Markus Grompe, M.D., Ph.D., of Oregon Health Sciences University in Portland, Ore., report that they have identified and cloned that sixth gene, dubbed FANCD2. In the second paper, the groups demonstrate that, once activated, FANCD2 gives rise to a protein that switches on BRCA1.

"FANCD2 turns out to be the missing link between the Fanconi anemia enzyme and the switching on of BRCA1," D'Andrea says. "When FANCD2 is activated, it serves as a 'zip code' that sends the FANCD2 protein to BRCA1. Once bound, the FANCD2 and BRCA1 proteins cooperate in DNA repair."

When all the Fanconi genes and BRCA1 are normal - as in the vast majority of the population - the result of this chain of events is the repair of damaged DNA within cells. When any of those genes in the pathway are flawed, BRCA1 is not activated, causing genetic damage to build up in cells and setting the stage for cancer.

While the discovery may lead to new tests for determining who is at risk for inherited breast cancer, it could result in new therapies as well. "It might be possible to design a drug that amplifies this pathway, accelerating the repair work of BRCA1 and reducing the chances that breast cancer will occur in people with a genetic risk for it," D'Andrea says. "Much work, however, remains to be done before such therapies become a reality."

The study comes after a year in which D'Andrea has reaped several honors for his work. In the past 12 months, he has been promoted to full professor at Harvard Medical School, was named the Ted Williams Senior Investigator at Dana-Farber, received a Distinguished Clinical Scientist Award from the Doris Duke Foundation, and won the E. Mead Johnson Award for 2001.

Dana-Farber Cancer Institute (http://www.danafarber.org) is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), a designated comprehensive cancer center by the National Cancer Institute.


Story Source:

The above story is based on materials provided by Dana-Farber Cancer Institute. Note: Materials may be edited for content and length.


Cite This Page:

Dana-Farber Cancer Institute. "Scientists Discover "Missing Link" Between Rare Disease And Inherited Forms Of Breast Cancer." ScienceDaily. ScienceDaily, 16 February 2001. <www.sciencedaily.com/releases/2001/02/010216081820.htm>.
Dana-Farber Cancer Institute. (2001, February 16). Scientists Discover "Missing Link" Between Rare Disease And Inherited Forms Of Breast Cancer. ScienceDaily. Retrieved July 24, 2014 from www.sciencedaily.com/releases/2001/02/010216081820.htm
Dana-Farber Cancer Institute. "Scientists Discover "Missing Link" Between Rare Disease And Inherited Forms Of Breast Cancer." ScienceDaily. www.sciencedaily.com/releases/2001/02/010216081820.htm (accessed July 24, 2014).

Share This




More Health & Medicine News

Thursday, July 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com
Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Newsy (July 24, 2014) Sheik Umar Khan has treated many of the people infected in the Ebola outbreak, and now he's become one of them. Video provided by Newsy
Powered by NewsLook.com
Condemned Man's US Execution Takes Nearly Two Hours

Condemned Man's US Execution Takes Nearly Two Hours

AFP (July 24, 2014) America's death penalty debate raged Thursday after it took nearly two hours for Arizona to execute a prisoner who lost a Supreme Court battle challenging the experimental lethal drug cocktail. Duration: 00:55 Video provided by AFP
Powered by NewsLook.com
China's Ageing Millions Look Forward to Bleak Future

China's Ageing Millions Look Forward to Bleak Future

AFP (July 24, 2014) China's elderly population is expanding so quickly that children struggle to look after them, pushing them to do something unexpected in Chinese society- move their parents into a nursing home. Duration: 02:07 Video provided by AFP
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