Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
GLOBETECH MEDIA
GLOBETECH PUBLISHING LLC

Three of Seven BRCA1 Mutations Definitively Linked to Cancer Development

By BiotechDaily International staff writers
Posted on 02 May 2013
Spanish researchers have definitively linked three mutations in the BRCA1 (breast cancer 1, early onset) gene to the development of hereditary forms of breast and ovarian cancer while another four mutations were found not to be implicated in cancer occurrence.

Mutations in the BRCA1 gene have been shown to confer a high risk for the development of breast or ovarian cancer. Statistical evidence suggests that women with a mutation in this gene have a 40% to 90% risk of developing ovarian cancer and between 20% and 70% risk of developing breast cancer.

Investigators at Bellvitge Biomedical Research Institute (Barcelona, Spain) and the Catalan Institute of Oncology (Barcelona, Spain) combined computer structural analysis prediction tools with an in vitro transcription activation (TA) assay to functionally assess a set of seven missense variants of uncertain significance (VUS) labeled Q1409L, S1473P, E1586G, R1589H, Y1703S, W1718L and G1770V located in the C-terminal region of BRCA1.

They reported in the April 17, 2013, online edition of the journal PLoS One that the computer prediction programs gave discrepant results making their interpretation difficult. On the other hand, structural analysis of the three variants located in the BRCT domains (Y1703S, W1718L, and G1770V) revealed significant alterations of BRCT structure. The TA assay showed that variants Y1703S, W1718L, and G1770V dramatically compromised the transcriptional activity of BRCA1, while variants Q1409L, S1473P, E1586G, and R1589H behaved like wild-type BRCA1. Thus, three of the VUS had significant functional impact and may represent pathogenic BRCA1 variants while the remaining four did not have a functional impact.

"In the functional study we analyzed in vitro one of the key functions of BRCA1: regulation of transcription," said senior author Dr. Conxi Lázaro, coordinator of the molecular diagnostics units of the hereditary cancer program at the Catalan Institute of Oncology. "The analysis involves the generation of mutants of all variants in specific vectors to assess the transcriptional activity of the mutant compared to the control activity of the wild-type sequence of the BRCA1 gene. Now we know a lot of genetic alterations in BRCA1 that are clearly pathogenic alterations, neutral alterations, and sequence polymorphisms, but genetic diagnostic studies also identify changes in the DNA sequence, which we do not know its biological significance."

"To the individuals who carry the mutation we can offer a comprehensive clinical monitoring and the possibility of reproductive options, such as prenatal or preimplantation diagnosis," said Dr. Lazaro, "while members of the family who do not have the mutation can be considered as general population."

Related Links:

Bellvitge Biomedical Research Institute
Catalan Institute of Oncology



Channels

Drug Discovery

view channel
Image: Researchers have attached two drugs—TRAIL and Dox—onto graphene strips. TRAIL is most effective when delivered to the external membrane of a cancer cell, while Dox is most effective when delivered to the nucleus, so the researchers designed the system to deliver the drugs sequentially, with each drug hitting a cancer cell where it will do the most damage (Photo courtesy of Dr. Zhen Gu, North Carolina State University).

Anticancer Drug Delivery System Utilizes Graphene Strip Transporters

The ongoing search by cancer researchers for targeted drug delivery systems has generated a novel approach that uses graphene strips to transport simultaneously the anticancer agents TRAIL (tumor necrosis... Read more

Biochemistry

view channel

Blocking Enzyme Switch Turns Off Tumor Growth in T-Cell Acute Lymphoblastic Leukemia

Researchers recently reported that blocking the action of an enzyme “switch” needed to activate tumor growth is emerging as a practical strategy for treating T-cell acute lymphoblastic leukemia. An estimated 25% of the 500 US adolescents and young adults diagnosed yearly with this aggressive disease fail to respond to... Read more

Therapeutics

view channel
Image: Cancer cells infected with tumor-targeted oncolytic virus (red). Green indicates alpha-tubulin, a cell skeleton protein. Blue is DNA in the cancer cell nuclei (Photo courtesy of Dr. Rathi Gangeswaran, Bart’s Cancer Institute).

Innovative “Viro-Immunotherapy” Designed to Kill Breast Cancer Cells

A leading scientist has devised a new treatment that employs viruses to kill breast cancer cells. The research could lead to a promising “viro-immunotherapy” for patients with triple-negative breast cancer,... Read more

Lab Technologies

view channel
Image: MIT researchers have designed a microfluidic device that allows them to precisely trap pairs of cells (one red, one green) and observe how they interact over time (Photo courtesy of Burak Dura, MIT).

New Device Designed to See Communication between Immune Cells

The immune system is a complicated network of many different cells working together to defend against invaders. Effectively combating an infection depends on the interactions between these cells.... Read more

Business

view channel

Program Designed to Provide High-Performance Computing Cluster Systems for Bioinformatics Research

Dedicated Computing (Waukesha, WI, USA), a global technology company, reported that it will be participating in the Intel Cluster Ready program to deliver integrated high-performance computing cluster solutions to the life sciences market. Powered by Intel Xeon processors, Dedicated Computing is providing a range of... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.