Charis Eng, MD, PhD, FACP

2009-2010 BCRF Project:
Apart from PTEN, Dr. Eng and her colleagues believe that SDHB and SDHD, which relate to mitochondrial energy production, may be new genes which when altered cause susceptibility to Cowden syndrome. They have found and confirmed that SDHB and SDHD mitochondrial subunit genes do play a role in lending heritable predisposition to breast and other cancers. In the last funding period, they also have preliminary hints that these two genes may help modulate breast cancer risk in individuals with alterations in another breast cancer predisposition gene, PTEN. Therefore, they wish to continue their patient-oriented research to validate our hypothesis that SDHx are important susceptibility genes for CS/CS-like, and alterations in SDHx could increase the risk of breast cancer in those with PTEN mutation. They hope to approach this objective by patient-oriented research, in vitro (in the test-tube) analysis and begin the construction of a laboratory model. However, there remain CS/CS-like individuals, many with breast cancers, who have neither PTEN nor SDH mutations/variants, and in the upcoming year, the researchers also seek to explore whether non-traditional mechanisms of PTEN shut off can act as predisposition alleles.

Individuals with alterations in the PTEN breast and thyroid cancer predisposition genes have one of two copies altered (heterozygous mutation) in the germline (every cell of the body). The transcript (messenger directed by the PTEN gene) expression of both copies of the gene should either be no different than those without alterations or should be half of normal dosage. The Eng team has found a subset of individuals with heterozygous germline PTEN mutations with PTEN expression less than half. This is due to more rapid degradation of both the mutant copy of the PTEN transcript as well as the normal copy of the transcript from patients compared to PTEN transcript in individuals with two normal copies of the PTEN gene.

Mid-Year Progress Report:
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 and her team have found that mutations in two mitochondrial genes, SDHB and SDHD, account for a subset of CS and CS-like (CSL) individuals without PTEN mutations. During this period, they also have found that SDHB/D alterations do occur in PTEN mutation positive CS and CSL individuals and appear to further elevate their already elevated risks of breast and thyroid cancers.

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.