Featured Research

from universities, journals, and other organizations

BROCA sequencing approach evaluates all 24 genes implicated in breast cancer

Date:
October 24, 2013
Source:
American Society of Human Genetics
Summary:
Comprehensive testing for all known inherited breast cancer gene mutations explains occurrence of the cancer in women with normal BRCA genes and family history of the disease.

Since 1994, many thousands of women with breast cancer from families severely affected with the disease have been tested for inherited mutations in BRCA1 and BRCA2. The vast majority of those patients were told that their gene sequences were normal.

Related Articles


With the development of modern genomics sequencing tools, the discovery of additional genes implicated in breast cancer and the change in the legal status of genetic testing for BRCA1 and BRCA2, it is now possible to determine how often families in these circumstances actually do carry cancer-predisposing mutations in BRCA1, BRCA2, or another gene implicated in breast cancer, despite the results of their previous genetic tests.

This was the challenge addressed by Mary-Claire King, Ph.D., American Cancer Society Professor of Medicine and Genome Sciences, and Tomas Walsh, Ph.D., Associate Research Professor of Medical Genetics, both at the University of Washington, Seattle. They conducted complete genomic sequencing of all genes implicated in breast cancer on DNA samples from breast cancer patients who had normal BRCA1 and BRCA2 commercial test results. The commercial testing occurred because the patients had a severe family history of breast cancer, defined as a family with three or more relatives affected by breast or ovarian cancer.

The results were presented today, Oct. 24, by Dr. Walsh at the American Society of Human Genetics 2013 meeting in Boston.

The researchers found that over 25 percent of index patients with normal results from commercial testing of BRCA1 and BRCA2, but with families severely affected by breast cancer, could be resolved by sequencing all genes known to be involved in breast cancer.

Sequencing was carried out using BROCA, an openly available, targeted capture and genomic sequencing approach that was developed and validated by Drs. Walsh and King in 2010. BROCA detects all single base substitutions, insertions and deletions and copy number variants in all 24 genes implicated in breast cancer.

The researchers used BROCA to test 2,285 members of 743 families with at least three relatives with breast or ovarian cancer. Each of those families included at least one woman with breast cancer who had received normal results from complete commercial genetic testing for BRCA1 and BRCA2. The commercial tests were based on both Sanger sequencing and supplementary testing for large genomic rearrangements in both genes.

Of the 743 families, 26% (191) were resolved by BROCA. The 191 resolved families were found to harbor 149 different inherited, damaging mutations in 18 distinct genes.

Of the 191 resolved families, 35% (66) carried inherited, damaging mutations in BRCA1 or BRCA2 that were not detected by commercial sequencing. The scientists explained that the BRCA mutations were not detected by commercial testing for one of two reasons. In some families, the patient who was tested had normal sequences of BRCA1 and BRCA2, but her relatives with breast cancer carried a mutation in one of those genes. In other families, both the patient who was tested and her relatives carried a BRCA1 or BRCA2 mutation of a type not reported by commercial testing.

In the remaining families resolved by BROCA, 65% (125) carried inherited, damaging mutations in genes other than BRCA1 or BRCA2 that also have been associated with breast cancer. The researchers found that 18 different genes harbored cancer-predisposing mutations in those 125 families, but each affected person carried a mutation in only one gene.

Carriers of mutations in some of the genes were at significantly increased risk of ovarian cancer for women and increased risk of breast cancer in men as well as in women.

Comprehensive testing is rapidly becoming more widespread. "It is important to determine more precisely the risks associated with damaging mutations in each of these genes so as to incorporate them most effectively into clinical care," Dr. Walsh said.

These assessments are best undertaken by sharing data across all centers that carry out genetic testing for breast and ovarian cancer risk, said Dr. King.


Story Source:

The above story is based on materials provided by American Society of Human Genetics. Note: Materials may be edited for content and length.


Cite This Page:

American Society of Human Genetics. "BROCA sequencing approach evaluates all 24 genes implicated in breast cancer." ScienceDaily. ScienceDaily, 24 October 2013. <www.sciencedaily.com/releases/2013/10/131024090239.htm>.
American Society of Human Genetics. (2013, October 24). BROCA sequencing approach evaluates all 24 genes implicated in breast cancer. ScienceDaily. Retrieved October 31, 2014 from www.sciencedaily.com/releases/2013/10/131024090239.htm
American Society of Human Genetics. "BROCA sequencing approach evaluates all 24 genes implicated in breast cancer." ScienceDaily. www.sciencedaily.com/releases/2013/10/131024090239.htm (accessed October 31, 2014).

Share This



More Health & Medicine News

Friday, October 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Fauci Says Ebola Risk in US "essentially Zero"

Fauci Says Ebola Risk in US "essentially Zero"

AP (Oct. 30, 2014) NIAID Director Anthony Fauci said the risk of Ebola becoming an epidemic in the U.S. is essentially zero Thursday at the Washington Ideas Forum. He also said an Ebola vaccine will be tested in West Africa in the next few months. (Oct. 30) Video provided by AP
Powered by NewsLook.com
Nurse Defies Ebola Quarantine With Bike Ride

Nurse Defies Ebola Quarantine With Bike Ride

AP (Oct. 30, 2014) A nurse who vowed to defy Maine's voluntary quarantine for health care workers who treated Ebola patients followed through on her promise Thursday, leaving her home for an hour-long bike ride. (Oct. 30) Video provided by AP
Powered by NewsLook.com
Pot-Infused Edibles Raise Concerns in Colorado

Pot-Infused Edibles Raise Concerns in Colorado

AFP (Oct. 30, 2014) Colorado may have legalized marijuana for recreational use, but the debate around the decision still continues, with a recent - failed - attempt to ban cannabis-infused edibles. Duration: 01:53 Video provided by AFP
Powered by NewsLook.com
British Navy Ship Arrives in Sierra Leone With Ebola Aid

British Navy Ship Arrives in Sierra Leone With Ebola Aid

AFP (Oct. 30, 2014) The British ship RFA ARGUS arrived in Sierra Leone to deliver supplies and equipment to help the fight against Ebola. Duration: 00:42 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:

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