Fergus J. Couch, PhD

On behalf of Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA)
Dr. Couch is coordinating Stage 1 of a genome wide study of BRCA1 mutation carriers which proposes to identify commonly inherited genetic alterations that determine whether a woman with a BRCA1 mutation will develop cancer in her lifetime or not. These alterations may also allow the researchers to distinguish those who will develop cancer at a young age from those who will develop cancer at a later age. If identified, these older women may not have to undergo prophylactic mastectomy and oophorectomy to reduce their cancer risks until later in life.

Furthermore, by identifying the genetic events that promote cancer development it should be possible to target these genes and alterations for the purposes of cancer prevention. The researchers are focused on BRCA1 carriers because the breast tumors developing in these women (estrogen receptor negative, progesterone receptor negative and Her2 negative) represent a unique subset of breast tumors about which little is known. Thus, a genome wide study focused on this population can help to explain the etiology of the so-called triple negative breast cancers.

Because the study involves a whole genome screen, it is highly likely that novel genetic risk factors for BRCA1 mutation carriers will be identified. In addition these risk factors will likely be directly relevant to patients who develop basal breast cancer because the great majority of BRCA1 carriers present with this type of disease. The project involves 35 groups from the U.S., Canada, Europe and Australia who form the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), who have come together to identify common genetic alterations than modify risk in carriers of both BRCA1 and BRCA2 mutations.

Mid-Year Progress Report:
This project is studying common genetic alterations in the human genome among women with mutations in the BRCA1 breast and ovarian cancer predisposition genes in order to identify the alterations that modify the risk of breast cancer. DNA samples from over 3,000 women have been collected and the samples that will be used in the first stage of the genetic testing of alterations have been selected.

Bio:
Fergus J. Couch is an Associate Professor in the Department of Laboratory Medicine and Pathology in the Mayo Clinic College of Medicine. He obtained his undergraduate and Ph.D degrees from University College Cork, Ireland and received postdoctoral training under the mentorship of Francis S. Collins at the University of Michigan and Barbara L. Weber at the University of Pennsylvania. He is the vice-chair of the Division of Experimental Pathology and the deputy director of the breast cancer research program at the Mayo Clinic.

Dr. Couch has had a long-standing interest in the genetics of breast cancer following his involvement in the initial characterization of the BRCA1 and BRCA2 genes as a postdoctoral fellow. Dr. Couch is taking a multidisciplinary approach to characterization of genetic factors associated with breast cancer. Much of his work is focused on identification of common genetic risk factors for breast cancer and genetic modifiers of breast cancer risk in BRCA1 and BRCA2 mutation carriers. In addition, he leads an international consortium that is using laboratory and epidemiological approaches to determine which unclassified variants in BRCA1 and BRCA2 predispose to cancer. Dr. Couch is also studying how BRCA2 and a number of candidate oncogenes from a region of gene amplification on chromosome 17 contribute to breast cancer using animal models and cell biology approaches. His studies of these genes have led to a specific interest in the contribution of defects in cell division to breast cancer.