Mary-Claire King, PhD
American Cancer Society Professor
Departments of Medicine and Genome Sciences
University of Washington, Seattle, WA
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Co-Investigators:
Ephrat Levy-Lahad, MD, Shaare Zedek Medical Center, Jerusalem, Israel and
Moien Kanaan, PhD, Bethlehem University, Palestinian Authority
Drs. King, Levy-Lahad, and Kanaan have now enrolled over 640 breast cancer patients of Palestinian origin in their studies. They found mutations in known breast cancer genes in 8/48 (17%) patients who were analyzed for all known cancer genes. This high proportion is consistent with the team’s hypothesis that since breast cancer is less frequent in the Palestinian population, a larger proportion of cases will be due to an inherited predisposition. They will now be analyzing all known breast cancer genes in an additional 176 cases with family history. They expect to identify new mutations, and in cases where no mutations in known genes are identified, they will search for novel breast cancer genes.
Mid-year Progress: This research team has now enrolled over 700 breast cancer patients of Palestinian origin and has begun their analysis by next generation sequencing. In the first 48 patients evaluated, they found inherited cancer-predisposing mutations in 17% of patients, in BRCA1, BRCA2, and four other genes. This proportion of patients harboring damaging mutations is among the highest seen in any population. It is consistent with the team's hypothesis that since breast cancer is less frequent and occurs in younger women in the Palestinian population, a larger proportion of cases will be due to inherited predisposition. They will analyze all known breast cancer genes in an additional 200 cases with family history or young age at diagnosis. The investigators expect to identify new mutations, and in cases where no mutations in known genes are identified, they will search for novel breast cancer genes.
2)The New York Breast Cancer Study
Co-Investigator: Joan H. Marks, MS, New York Breast Cancer Study at Sarah Lawrence College, Bronxville, NY
The goal of the New York Breast Cancer Study is to identify all genes responsible for inherited predisposition to breast cancer in the Ashkenazi Jewish population and by extension among women of all ancestries. To discover these genes, Dr. King’s team uses genomic sequencing to evaluate DNA from women who have developed breast cancer and from their unaffected relatives. In 2011-2012, they refined their genomics approach, named BROCA, for targeted genomic capture and sequencing for all genes for inherited predisposition to breast cancer. This approach is a “one-stop shop” that enables the simultaneous complete evaluation of 24 breast cancer genes from a small DNA sample from a participant. Researchers led by Dr. King are using BROCA to sequence DNA from participants in the New York Breast Cancer Study. The goal is to identify heretofore unknown mutations, in both known and previously unknown genes, that may explain the breast cancers of participants with none of the more common mutations in BRCA1 or BRCA2.
Mid-year Progress: With BCRF support, Dr. King's team developed the novel approach to screening called BROCA, which is based on targeted genomic capture and ultra-high-throughput next-generation sequencing. It is more complete, faster, and far less expensive than current commercial approaches. BROCA is now in clinical use at the University of Washington hospital and elsewhere and is the method with which this group is screening DNA from participants in the New York Breast Cancer Study.
In this phase of the New York Breast Cancer Study, the investigators are addressing two questions. First, how often do mutations in BRCA1 and BRCA2 other than the three common Ashkenazi Jewish mutations occur among women in this population with breast cancer? They had previously described the frequencies and risks due to the common AJ mutations in BRCA1 and BRCA2 in the original publications of the NYBCS. And second, how often do mutations in breast-cancer-predisposing genes other than BRCA1 and BRCA2 occur among Ashkenazi Jewish women with breast cancer? Their goal is to identify all mutations, in both known and previously unknown genes, that may explain the breast cancers of participants with none of the more common mutations in BRCA1 or BRCA2.
Bio:
Mary-Claire King is American Cancer Society Research Professor of Genetics and Medicine at the University of Washington. Work in her lab focuses on genetic analysis of breast and ovarian cancer. Dr. King was the first to prove that breast cancer is inherited in some families. She is now studying BRCA1 and BRCA2 and searching for other breast and ovarian cancer genes. Her other medical research interests include genetic analysis of inherited deafness and systemic lupus erythematosus. Her lab is also interested in human genetic diversity and evolution, and in the application of DNA sequencing to human rights problems.
Dr. King received her BA in Mathematics from Carleton College, her PhD in Genetics from University of California at Berkeley, and her postdoctoral training at UC San Francisco. She has served on the National Commission on Breast Cancer of the President's Cancer Panel, the advisory board of the National Institutes of Health (NIH) Office of Research on Women's Health, the Council of the NIH Fogarty Center, the advisory board of the National Action Plan for Breast Cancer, the NIH Breast Cancer Program Review Group, the Board of Scientific Counselors of National Cancer Institute, the Board of Scientific Counselors of Memorial Sloan-Kettering Cancer Center, the National Research Council committee to advise the Department of Defense on their Breast Cancer Research Program, and many NIH study sections. Abroad, she has served as Consultant to the Commission on the Disappearance of Persons of the Republic of Argentina and has carried out DNA identifications for the United Nations War Crimes Tribunal.
Dr. King has been elected to Phi Beta Kappa and Sigma Xi, as a Fellow of the AAAS, to the Institute of Medicine (and its Council), to the American Academy of Arts and Sciences,and as honorary chair for Washington state for the 50th Anniversary of the United Nations. She has received the Clowes Award for Basic Research from the American Association for Cancer Research, the Jill Rose Award from The Breast Cancer Research Foundation, the Brinker Award from the Komen Foundation, a Woman of the Year Award from Glamour magazine, and honorary doctorates from Carleton, Smith, Bard, and Dartmouth Colleges. In 2012, Dr. King was elected as President of the American Society of Human Genetics and elected to the American Philosophical Society.
Dr. King has one daughter, Emily, who lives and works in Berkeley.
