Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING
JIB
GLOBETECH PUBLISHING

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



comments powered by Disqus

Channels

Drug Discovery

view channel

Ibuprofen May Restore Immune Function in Older Individuals

New research suggests that macrophages from the lungs of old mice respond differently to infections than those of young mice, and ibuprofen given to the mice reversed these changes. New research using lab mice suggests that the solution to more youthful immune function might already be a common over-the-counter pain reliever.... Read more

Therapeutics

view channel
Image: Hair follicle (blue) being attacked by T cells (green) (Photo courtesy of Christiano Lab/Columbia University Medical Center).

Hair Restoration Method Clones Patients’ Cells to Grow New Hair Follicles

Researchers have developed of a new hair restoration approach that uses a patient’s cells to grow new hair follicles. In addition, the [US] Food and Drugs Administration (FDA) recently approved a new drug... Read more

Lab Technologies

view channel
Image: Leica Microsystems launches the inverted research microscope platform Leica DMi8 (Photo courtesy of Leica Microsystems).

New Inverted Microscope Designed to Readily Adapt to Changing Research Demands

A new inverted microscope for biotech and other life science laboratories was designed to readily accommodate modifications and upgrades to allow it to keep current with changing research demands and interests.... Read more

Business

view channel

Partnership Established to Decode Bowel Disease

23andMe (Mountain View, CA,USA), a personal genetics company, is collaborating with Pfizer, Inc. (New York, NY, USA), in which the companies will seek to enroll 10,000 people with inflammatory bowel disease (IBD) in a research project designed to explore the genetic factors associated with the onset, progression, severity,... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.