About My Health Careers Internship MedBlogs Contact us
Medindia LOGIN REGISTER
Advertisement

Potential Breast Cancer Susceptibility Gene Identified Through Network Approach

by Medindia Content Team on October 16, 2007 at 3:37 PM
Font : A-A+

Potential Breast Cancer Susceptibility Gene Identified Through Network Approach

Scientists at the Dana-Farber Cancer Institute and an international group of collaborators have used data obtained from genes involved in inherited forms of breast cancer to identify a novel gene potentially linked to the disease.

Their approach, described in a study posted online by the journal Nature Genetics, used advanced laboratory techniques plus novel "data mining" approaches to discover new cancer-related genes. The technique may help researchers find genes associated with other forms of cancer as well, plus non-cancerous conditions that have a genetic basis, the authors state.

Advertisement

"More than 85 percent of breast cancer cases don't have a clear hereditary link. That is, they arise in women who haven't inherited an abnormal gene that increases their risk for the disease," says study co-author David E. Hill, PhD, of Dana-Farber's Center for Cancer Systems Biology (CCSB), where the research was based. "Science knows very little about which genes are involved in such cancers. Even among the 15 percent of breast cancers that do have a hereditary component, the responsible genes are known in only about three-quarters of cases.

"In this study," he continues, "We asked whether we could use the developing tools of network modeling [which probes the connections between genes and between proteins] and expression profiling [which focuses on patterns of gene activity] to guide us in finding candidate breast cancer genes."
Advertisement

Beginning with a list of four genes known to cause breast cancer when inherited in an abnormal form - BRCA1, BRCA2, ATM, and CHEK2 - the investigators gathered information from existing studies on connections between those "hub" genes and their gene partners. Those studies were of five kinds: expression profiles of genes whose activity mirrors that of the four hubs; surveys of gene activity when BRCA1 is shut down; published studies of biochemical interactions among proteins specified by the hub genes; expression profiles using yeast and worm versions of the hub genes; and the Dana-Farber team's own work in mapping protein-protein interactions.

"Although inherited and non-inherited (or 'somatic') breast cancers develop by markedly different mechanisms, it's likely that some of the same genes are involved," says study co-author Michael Cusick, PhD, of Dana-Farber. "We hope that by beginning with genes known to cause hereditary cases, we can derive clues to additional genes associated with hereditary disease as well as sporadic, non-inherited cases.

"The evidence we collected provides a 'global perspective' on the functions of breast cancer genes," he continues. "This technique enabled us to integrate existing data to find connections or patterns that others might have missed."

The approach enabled the researchers to narrow the list of candidate breast cancer-susceptibility genes from several thousand to about 150. Within that smaller group, they ranked the genes according how closely their activity resembled that of the four hubs, and therefore how likely they are to play a role in the disease. The highest-ranked gene that hadn't been previously investigated was one called HMMR.

Confirmation of the validity of the list came serendipitously, when researchers in the lab of Dana-Farber's David Livingston, MD, identified two genes as potentially related to breast cancer. Both were high on the team's list.

Surprisingly, one of these genes turned out to be the frog version of HMMR. Biochemical studies of both the human and frog proteins, carried out by the Livingston lab, confirmed the association of BRCA1 and HMMR.

More evidence came as a result of collaboration with scientists in New York and Michigan. Geneticists Stephen Gruber, MD, PhD, MPH, and Kenneth Offit, MD, at the University of Michigan and New York University, respectively, examined breast tumor samples from patients in Israel and New York and found that those with an error in HMMR were three to four times more likely to develop breast cancer than those without it. Interestingly the error didn't cause a faulty version of the HMMR protein to be made; rather it resulted in an over- or undersupply of the protein in breast cells.

"HMMR is a well-known gene; its job is to contribute to the function of the centrosome," a structure within cells that forms a "spindle" for chromosomes to align themselves during cell division, Cusick observes. Scientists have long known that cells with mutated BRCA1 often have abnormal spindles, but why this is so has been unclear. The fact that HMMR interacts strongly with BRCA1 on a functional level and is involved in spindle formation suggests a connection. Cells whose centrosomes assemble improperly often develop aneuploidy, a condition in which there is an extra or missing chromosome. That, in turn, can yield the kind of DNA mixups that result in cancer.

Study co-author Jeffrey Parvin, MD, PhD, of Brigham and and Women's Hospital provided additional evidence of a tie between HMMR and BRCA1. He showed that cells without either gene are apt to have problems with centrosome formation.

Hill and Cusick note that the newfound connection between HMMR abnormalities and breast cancer does not mean it is an inherited breast gene. It is likely to be, instead, a breast cancer susceptibility gene in which an abnormality may result - depending on conditions that aren't yet known - in an increased breast cancer risk.

The investigators also say that the technique used in this study can be applied to any form of cancer or other genetically based disease in which genes for some forms of the disease are known while others are not. "It enables us to search for new cancer genes in an unbiased way, with no preconceptions of which ones may turn out to be involved in the disease," Hill says. "By combining the results of multiple studies on gene networks, we can let the data lead us to the answers. It provides a new avenue of research with a high likelihood of success."

Source: Eurekalert
GAN/S
Advertisement

Advertisement
News A-Z
A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
Advertisement
News Category
What's New on Medindia
Fermented Skin Care
Television Binge-Watching May Boost the Risk of Deadly Blood Clots
Western Diet may Augment the Risk of Autoimmune Diseases
View all

Medindia Newsletters Subscribe to our Free Newsletters!
Terms & Conditions and Privacy Policy.

More News on:
Women and Cancer DNA Finger Printing Breast Biopsy Pagets disease of the breast Mastitis Cancer and Homeopathy Breast Cancer Facts Cancer Facts Cancer Breasts - Structures and Types 

Recommended Reading
Researchers Identify New Gene That may Raise the Risk of Breast Cancer
A multi-centre international team of researchers has uncovered a new gene that may raise a woman's ....
Breast Biopsy
Breast biopsy involves removing a sample of breast tissue to determine whether it is cancerous or .....
Breasts - Structures and Types
Different stages of breast development in women and an in-depth look at the breast/bust and its ......
DNA Finger Printing
DNA fingerprinting is a technique which helps forensic scientists and legal experts solve crimes, id...
Mastitis
Mastitis is a common cause of tenderness, swelling and pain in breast, owing to inflammation in the ...
Pagets disease of the breast
A detailed description of the Paget's disease of the breast, characteristic signs and symptoms, dete...
Women and Cancer
Cancer is one of the frequently talked about and most feared disease that falls under the genre of l...

Disclaimer - All information and content on this site are for information and educational purposes only. The information should not be used for either diagnosis or treatment or both for any health related problem or disease. Always seek the advice of a qualified physician for medical diagnosis and treatment. Full Disclaimer

© All Rights Reserved 1997 - 2022

This site uses cookies to deliver our services. By using our site, you acknowledge that you have read and understand our Cookie Policy, Privacy Policy, and our Terms of Use
open close
CONSULT A DOCTOR
I have read and I do accept terms of use - Telemedicine

Advantage Medindia: FREE subscription for 'Personalised Health & Wellness website with consultation' (Value Rs.300/-)