OHSU Researchers Link Breast Cancer Gene to Fanconi Anemia

06/11/02    Portland, Ore.

Disease impacts one of Oregon's most prominent families.

An international research team that includes Oregon Health & Science University scientists has discovered that a breast cancer gene, known to interact with the genes that cause Fanconi anemia (FA), can itself cause the rare disease. The finding helps scientists better understand the chemical pathways in the body involved in the development of FA. This information should help physicians better diagnose the disease, and assist researchers as they search for new therapies or a possible cure. While FA is a rare disease, Scientists also believe this information provides promise for research into breast, ovarian and pancreatic cancers. The research is published in the June 13 online edition of the journal Science.

The gene at the center of this research is BRCA2. Past investigations have shown that in addition to being one of the culprits behind familial breast cancer, BRCA2 can also cause ovarian and pancreatic cancers. In fact, researchers believe the gene may be the starting point for tumors associated with these cancers. This latest research shows that the gene is also involved in the development of two forms of FA. Up to this point, no genetic link to these two forms of the disease had been found. Because FA is a recessive disorder, people must be born with two mutated BRCA2 genes, one from their mother and one from their father, to develop the disease.

"We suspected that BRCA2 played an important role in Fanconi anemia because cells from FA patients and BRCA-mutated cells behaved so similarly," said Markus Grompe, M.D, professor of molecular and medical genetics, and pediatrics in the OHSU School of Medicine, and leader of the OHSU research team. "We also suspected that there was a chance the gene could do more than simply interact with the established FA genes. Now we know for sure of its importance."

Barbara Cox, Ph.D., research assistant professor of molecular and medical genetics, and geneticist Susan Olson, Ph.D., both in the OHSU School of Medicine, worked with Grompe at OHSU on the finding.

FA is associated with multiple severe birth defects, as well as a predisposition to cancer. At least seven genes are responsible for FA. So far six of these genes had been identified and cloned, including the cloning of the FANCD2 gene at OHSU in 2001.With this latest finding, BRCA2 and another cancer gene known as BRCA1 have both been linked with the six FA genes in a common chemical pathway that causes the disease.

"Cancer occurs earlier in FA patients than in families with BRCA2 gene defects and also affects different tissues, primarily blood," said Grompe.

While FA is rare disease, affecting about 3,000 people worldwide, one of Oregon's most prominent families has lost two members to the genetic disorder. In 1991, 12-year-old Katie Frohnmayer died from complications caused by the disease, and 24-year-old Kirsten Frohnmayer died in 1997, two years after receiving a bone marrow transplant. Both are daughters of David Frohnmayer, president of the University of Oregon, and his wife, Lynn. The Frohnmayers and the Fanconi Anemia Research Fund, which the family organized in 1989, have helped OHSU and several other institutions around the world to further the understanding of FA.

The Frohnmayer family is excited about the wide-reaching implications that this discovery may have. They made the following statement in response to the announcement:

"This is a very major breakthrough in the understanding of cancers of the breast, ovaries and pancreas. It is directly traceable to funded research and collaborations developed at a scientific meeting of the Fanconi Anemia Research Fund. This welcome discovery is further evidence of the increasingly central role of FA science in cancer research generally. The thousands of Oregonians who contributed to the fund through the years should be extremely heartened."

This latest research was funded by the Fanconi Anemia Research Fund and the National Heart Lung and Blood Institute, a component of the National Institutes of Health.

Other collaborators in this study included researchers at Harvard Medical School; Free University Medical Center in Amsterdam, The Netherlands; Academic Hospital Maastricht, The Netherlands; and Sapporo Medical University School of Medicine, Sapporo, Japan.

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