Corporate Banner
Satellite Banner
Stem Cells, Cellular Therapy & Biobanking
>
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Researchers Develop a Method to Evaluate Variations Identified in Breast Cancer Susceptibility Genes

Published: Tuesday, July 08, 2008
Last Updated: Tuesday, July 08, 2008
Bookmark and Share
The researchers believe that the new test could become a useful and viable tool for genetic counselors, and may have implications beyond cancer.

Using mouse embryonic stem cells, researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, have developed a new method to evaluate which mutations, or changes, in a gene known to increase breast cancer susceptibility, may lead to cancer.

The new test, called a functional assay, is more comprehensive and reliable than most current methods. This new test could become a useful and viable tool for genetic counselors, and may have implications beyond cancer.

The researchers believe that this test could also be useful for analyzing mutations found in other human disease-related genes. The results of this research will be published in the August 2008 issue of "Nature Medicine" and appear online July 6, 2008.

The proteins produced by the BRCA1 (BReast CAncer gene 1) and BRCA2 genes normally help to maintain the integrity of the cell's genetic material and function as tumor suppressors.

For over a decade, it has been known that alterations or defects in BRCA1, BRCA2, and their associated proteins are linked to increased risks of early onset familial breast and ovarian cancers. Studies have shown that a woman who has a mutation in one of these genes has a 35 to 85 percent risk of developing breast cancer by age 70, compared to the average American woman's lifetime risk of 12.3 percent.

Some individuals who want to know if they have inherited a mutation in a gene such as BRCA1 or BRCA2 that will increase their risk of developing breast or ovarian cancer are now choosing to go for genetic testing. Such tests can provide reassuring information to those who do not have harmful mutations, and can be helpful to those with harmful BRCA1 or BRCA2 mutations because when they know that they are at risk, they can work with their physicians to find the course of action that is best for them.

"However, think about those individuals who are tested and find out that they have an unclassified [minor or previously unknown] change in these genes, and they do not know what it means," said senior author Shyam Sharan, Ph.D. of the NCI's Center for Cancer Research.

"There is reason to believe that a significant number of women fall into this category, and our assay is likely to improve our understanding of unclassified mutations because it allows for analysis of all types of BRCA2 mutations," he added.

The new test looks for the functional significance of variations in BRCA2 using mouse embryonic stem cells. Mouse Brca2 is essential for the viability of mouse embryonic stem cells, and the assay is based on the ability of the human BRCA2 gene to complement the loss of the Brca2 gene in the mouse cells.

When introduced into a Brca2-deficient mouse embryonic stem cell in laboratory experiments, functionally normal human BRCA2 variants can compensate for the mouse Brca2 deficiency. On the other hand, harmful or deleterious variants of human BRCA2 do not have this ability, leading to their identification in this test.

Lead author of this paper, Sergey Kuznetsov, Ph.D., generated a set of cells in which one copy of the BRCA2 gene is inactivated or knocked out, and the other remains active but can be inactivated later. The researchers then introduced human genetic material, taking care to maintain all of the coding sequences and regulatory elements of the BRCA2 gene.

When genetic material with neutral variants of human BRCA2 was introduced, the researchers were able to subsequently remove the remaining copy of the mouse BRCA2 without compromising the viability of the cell.

The addition of genetic material with harmful variants, however, resulted in either cell death or deficient DNA repair. Therefore, the assay can be used to examine genetic material with minor or previously unknown variants. If a human variation does not alter the function of the mouse BRCA2, the risk of developing cancer is probably the same as that of the rest of the population, but if the change is disruptive, the risk of developing cancer increases significantly. The researchers are also working on development of a similar test for BRCA1 variants.

The researchers hope that other human disease gene functions may be evaluated in a similar fashion using this type of analysis. This represents an efficient method of analysis in which three to five gene variants can be analyzed in two to three months.

The researchers have provided preliminary validation of the functional assay by testing 17 variants, and have established the reproducibility of the technique for BRCA2. They caution, however, that only when this technique is FDA approved for use in a clinical setting will it be available to patients for diagnostic testing.

The technology behind this new assay is available for further research, and Dr. Sharan's laboratory is interested in collaborating with commercial organizations to further develop it as a product under the appropriate NIH agreements.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,000+ scientific posters on ePosters
  • More than 4,500+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

2011 Biospecimen Research Network (BRN) Symposium
The National Cancer Institute's (NCI) Biospecimen Research Network Symposium, "Advancing Cancer Research Through Biospecimen Science," will be held March 28-29, 2011, at the Bethesda North Marriott Hotel & Conference Center in Bethesda, MD
Friday, January 07, 2011
Scientists Identify Markers on Human Breast Cancer Cells Linked to Development of a Form of Breast Cancer
The scientists named these human cells with tumor-forming ability in mice, xenograft-initiating cells, or XIC.
Friday, May 21, 2010
Drug for Multiple Myeloma Demonstrated to Extend Disease-Free Survival
Patients receiving lenalidomide following a blood stem cell transplant had their cancer kept in check longer than placebo receiving patients.
Thursday, December 24, 2009
Cancer Immunotherapy Can Use Small Numbers of Stem-Like Immune Cells to Destroy Large Tumors in Mice
New approach to stimulating immune cells enhances their anticancer activity, resulting in a powerful anti-tumor response in mice.
Friday, June 26, 2009
Mouse Studies Show Gene Therapy Method Holds Promise in Targeting Tumor Blood Vessels for Destruction
Cancer researchers develop method for delivering a therapeutic gene specifically to the blood vessels of tumors in mice.
Thursday, December 18, 2008
Method of Gene Therapy Alters Immune Cells for Treatment of Advanced Melanoma
Technique may also apply to other common cancers.
Friday, September 01, 2006
Scientific News
AACR 2016: Cancer Immunotherapy and Beyond
At this year's meeting there was a palpable buzz around subjects ranging from microbiomics to the tumor microenvironment and cancer vaccines, big data to in vitro and in vivo modeling and drug delivery (to name just a few).
How Skeletal Stem Cells Form The Blueprint Of The Face
USC researchers discover that two types of molecular signals work to control where and when stem cells turn into facial cartilage.
Turning Skin Cells into Heart, Brain Cells
In a major breakthrough, scientists at the Gladstone Institutes transformed skin cells into heart cells and brain cells using a combination of chemicals.
Stem Cells Know How to Unwind
Research led by the Babraham Institute with collaborators in the UK, Canada and Japan has revealed a new understanding of how an open genome structure supports the long-term and unrestricted developmental potential in embryonic stem cells.
Growing Stem Cells More Safely
Nurturing stem cells atop a bed of mouse cells works well, but is a non-starter for transplants to patients – Brown University scientists are developing a synthetic bed instead.
Cell Transplant Treats Parkinson’s in Mice
A University of Wisconsin—Madison neuroscientist has inserted a genetic switch into nerve cells so a patient can alter their activity by taking designer drugs that would not affect any other cell.
Skin Cells Turned into Heart Cells and Brain Cells Using Drugs
In a scientific first, Gladstone researchers have used chemical drugs to convert skin cells into heart cells and brain cells, without adding any external genes.
Shape Of Tumor May Affect Whether Cells Can Metastasize
Illinois researchers found that the shape of a tumor may play a role in how cancer cells become primed to spread.
‘Mini-Brains’ to Study Zika
Novel tool expected to speed research on brain and drug development.
Cytokine Triggers Immune Response at Expense of Blood Renewal
Research highlights promise of Anti-IL-1 drugs to treat chronic inflammatory disease.
SELECTBIO

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,500+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!