Co-Director of The New York Breast Cancer Study
Sarah Lawrence College
Bronxville, New York
Co-Investigator: Mary-Claire King, PhD, New York Breast Cancer Study at the University of Washington, Seattle, WA
The goal of the New York Breast Cancer Study (NYBCS) is to identify all genes responsible for inherited predisposition to breast cancer among women of Ashkenazi Jewish ancestry and by extension among women of all ancestries. To discover these genes, these researchers use genomic sequencing to evaluate DNA from women who have developed breast cancer and from their relatives. In 2012-2013, they studied DNA from NYBCS participants who had no mutations in BRCA1 or BRCA2 but whose families were nonetheless severely affected with breast cancer.
Dr. King's team discovered that breast cancer in approximately one-fifth (21%) of these families could be explained by inherited mutations in other genes. This discovery suggests that in future, clinical testing for inherited predisposition to breast cancer should include other genes in addition to BRCA1 and BRCA2.
But what next? While it is obviously important and useful to learn the causes of breast cancer in a fifth of unresolved families, this group hopes to solve them all. The next step of the NYBCS will be to search, genome-wide, for mutations in regulatory regions that may influence proper timing and expression of critical genes.
The goal of the New York Breast Cancer Study is to identify all genes responsible for inherited predisposition to breast cancer among women of Ashkenazi Jewish ancestry and by extension among women of all ancestries. To discover these genes, Drs. King and Marks use genomic sequencing to evaluate DNA from women who have developed breast cancer and from their relatives. In fall 2013, they began a major genome-wide sequencing effort to identify mutations in regulatory regions that may influence timing and expression of genes critical to breast cancer. Thus far with this approach, the researchers have identified one class of mutation not previously detected in a breast cancer gene: mutation of a single DNA nucleotide deep inside a non-coding genomic region (an intron) that leads to appearance of a new coding region (an exon) in the wrong place. The new “impostor” coding region does not retain the reading frame of the normal gene, so introduces a premature truncation of the protein. The researchers expect multiple different, heretofore under-appreciated classes of mutations to be revealed by whole genome sequencing. Their hypothesis is that for mutation generally, and for mutations predisposing to breast cancer in particular, everything that can go wrong, will. They anticipate that each one of these events will be individually very rare, but that collectively they may not be rare. The practical importance of this phase of the NYBCS will be to reveal the range of mutations that can occur among women with breast cancer whose family history indicates that they likely have inherited predisposition to breast cancer, but who have normal sequences of all known breast cancer genes.
Joan H. Marks is Co-Director of The New York Breast Cancer Study, a research project examining the role of breast cancer genes in increasing the incidence of breast cancer in Ashkenazi Jewish women.
From 1972 to 1998 Joan Marks directed two unique graduate programs in health care at Sarah Lawrence College. The Human Genetics program, which she developed into the largest program in the country to educate genetic counselors, pioneered the field of genetic counseling and served as a model for 26 similar programs at universities in the U.S. and several others in Canada, Argentina, Australia, Puerto Rico, Taiwan, England and Israel. In 1979, Marks founded the Graduate Program in Health Advocacy at Sarah Lawrence, the first graduate degree program to train advocates who work within the complex health care delivery system in the U.S. to ensure the rights of patients and health care consumers.
Joan Marks has served on a number of advisory boards in medicine such as the American Board of Internal Medicine, the American Academy of Physicians and Patients, and the Women's Health Initiative of the National Institutes of Health. She has also chaired the Ethics Committee of the National Neurofibromatosis Association and is a member of their Clinical Care Advisory Board. She is the author of The Genetic Connection: How To Protect Your Family Against Genetic Disease and editor of Advocacy in Health Care: The Silent Constituency.
In 2003 Joan Marks became the first woman and first non-M.D. to receive the Excellence in Human Genetics Education Award, presented by the American Society of Human Genetics. In April, 2006, in recognition of her "enduring contributions to Sarah Lawrence College, and of her legacy as pioneer, educator, mentor, advocate and leader in genetic counseling," the College formally named its human genetics program the Joan H. Marks Graduate Program in Human Genetics.