Charis Eng, MD, PhD, FACP

2012-2013 BCRF Project:
(The von Mandl Family Award)

In the general population, it is estimated that one woman in eight is likely to develop breast cancer in her lifetime. In women born with mutations in their PTEN, SDHx, or KLLN genes, their lifetime risk increases from under 8 percent to as high as 85 percent. The ultimate goal of the research team led by Dr. Eng is to analyze processes that occur in genes and genetic mutations in order to predict with high accuracy those individuals at increased risk for breast and other gene-specific cancer(s). They aim to develop earlier and more accurate screening so that clinical interventions can be applied for the prevention of breast cancer. In addition, Dr. Eng and colleagues are also examining SDH-related reactive oxygen species (ROS) production as a target for therapeutic manipulation to prevent and treat breast cancer.

Mid-year Progress: Alterations (mutations) in the PTEN tumor suppressing gene are associated with a subset, but not all, individuals and families with Cowden syndrome (CS), who are predisposed to breast and thyroid cancers. Other genes must also predispose to breast and thyroid cancer. Dr. Eng's team has now validated with a very large number of patients that mutations in mitochondrial (energy-warehouse of a cell) genes SDHB, SDHC, and SDHD (SDHx) accounts for a subset of CS and CS-like (CSL) individuals independent of their PTEN mutation status. They found that CS and CSL individuals with SDHx alterations had increased prevalence of breast, thyroid, and renal cancers than those with PTEN mutations. Vitamin E, but not vitamin C, was able to rescue the defects in the cancer cells caused by SDHx alterations. Dr. Eng's laboratory had identified that individuals without PTEN or SDH alterations had a new way of shutting down a cancer suppressing gene KLLN (which is next to PTEN but reads backwards). CS/CSL individuals with KLLN shut-down had a three-fold increased frequency of breast cancer even over those with PTEN mutations. This will facilitate breast cancer risk assessment and management and genetic counseling. In this period, there are hints that KLLN mutations (not "shut down") play minor roles in CS/CSL but may be a new "weak" (complex) predisposition factor to non-syndromic breast cancer.

Bio:
Charis Eng is the Chairman and founding Director of the Genomic Medicine Institute of the Cleveland Clinic Foundation, founding Director and attending clinical cancer geneticist of the institute's clinical component, the Center for Personalized Genetic Healthcare, and Professor and Vice Chairman of the Department of Genetics at Case Western Reserve University School of Medicine.

She holds a joint appointment as Professor of Molecular Medicine at the Cleveland Clinic Lerner College of Medicine and is a full member of Cleveland Clinic's Taussig Cancer Center and of the CASE Comprehensive Cancer Center. Dr. Eng was recently honored with the Sondra J. and Stephen P. Hardis Endowed Chair in Cancer Genomic Medicine. She continues to hold an honorary appointment at the University of Cambridge. Dr. Eng's research interests may be broadly characterized as clinical cancer genetics translational research. Her work on RET testing in multiple endocrine neoplasia type 2 and the characterization of the widening clinical spectra of PTEN gene mutations have been acknowledged as the paradigm for the practice of clinical cancer genetics.

Dr. Eng grew up in Singapore and Bristol, UK and entered the University of Chicago at the age of 16. After completing an MD and PhD at its Pritzker School of Medicine, she specialized in internal medicine at Beth Israel Hospital, Boston and trained in medical oncology at Harvard's Dana-Farber Cancer Institute. She was formally trained in clinical cancer genetics at the University of Cambridge and the Royal Marsden NHS Trust, UK, and in laboratory-based human cancer genetics by Bruce Ponder, MB, PhD.

At the end of 1995, Dr. Eng returned to the Farber as Assistant Professor of Medicine, and in January, 1999 was recruited by The Ohio State University as Associate Professor of Medicine and Director of the Clinical Cancer Genetics Program. In 2001, she was honored with the conferment of the Davis Professorship and appointed Co-Director of the Division of Human Genetics in the Department of Internal Medicine. In 2002, she was promoted to Professor and Division Director, and was conferred the Klotz Endowed Chair. She moved to the Cleveland Clinic in Sept, 2005.

Dr. Eng has published over 290 peer reviewed original papers in such journals as the New England Journal of Medicine, JAMA, Lancet, Nature Genetics, Nature, Cell and Molecular Cell. She has received numerous awards and honors including election to the American Society of Clinical Investigation, to the Association of American Physicians and as Fellow of AAAS, the Doris Duke Distinguished Clinical Scientist Award and named a Local Legend from Ohio bestowed by the American Medical Women's Association in conjunction with the US Senate on women physicians who have demonstrated commitment, originality, innovation and/or creativity in their fields of medicine.

Dr. Eng is the 2005 recipient of the ATA Van Meter Award at the 13th International Thyroid Conference, the 2006 Ernst Oppenheimer Award of The Endocrine Society and the 2006 American Cancer Society John Peter Minton, MD, PhD Hero of Hope Research Medal of Honor. She was the North American Editor of the Journal of Medical Genetics from 1998 to 2005, is Senior Editor of Cancer Research and Associate Editor of the Journal of Clinical Endocrinology and Metabolism and of the American Journal of Human Genetics. Dr. Eng has been elected to a 3-year term on the Board of Directors of the American Society of Human Genetics and is serving a 5-year term on the Board of Scientific Directors of the National Human Genome Research Institute.