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Charis Eng, MD, PhD, FACP

Chairwoman, Genomic Medicine Institute, Cleveland Clinic
American Cancer Society Clinical Research Professor
Sondra J. and Stephen R. Hardis Chair of Cancer Genomic Medicine
Professor and Vice Chair, Department of Genetics
Case Western Reserve University
Cleveland, Ohio

Current Research

  • Seeking to understand the genetic risks that link Cowden Syndrome (CS) and a predisposition for breast cancer.
  • Ongoing studies are focused on identifying targets to block the effect of a mutation in a “tumor suppressor” gene called PTEN.
  • This research will inform more precise risk assessment and predictive information to aid in the prevention and management of breast cancer.

The breast cancer susceptibility genes, BRCA1 and BRCA2, are the most commonly mutated genes hereditary breast cancer, but mutations in other genes also predisposed individuals to breast cancer. Inherited mutations in a gene called PTEN cause a rare syndrome called Cowden Syndrome (CS). Individuals with CS also have a high rate of breast cancer. Dr. Eng is leading studies to understand the complex relationship between CS and breast cancer risk to identify new targets for prevention in this high-risk group.

Full Research Summary

Inherited mutations in the PTEN and SDHx “tumor suppressor” genes are common in individuals and families with Cowden syndrome (CS), a disease characterized by multiple non-cancerous, tumor-like growths. CS patients with PTEN or SDHx mutations have an increased risk of many cancers including breast cancer. Those with both PTEN and SDHx alterations have a significantly higher risk of breast cancer compared to those with either PTEN or SDHx mutations alone.

Dr. Eng's laboratory has shown that SDHx likely interferes with the cancer-fighting functions of PTEN by stimulating a variety of growth signals that promote breast cancer. Her current BCRF-supported study seeks to identify these mechanisms, which will provide risk assessment and predictive information to aid in the prevention and management of breast cancer.

In the coming year, Dr. Eng and her team will continue to search for new breast cancer risk modifiers in CS patients with PTEN mutations, as well as new breast cancer predisposition genes associated with CS/CS-like syndrome.

SDHx variants likely impact metabolism and cell fate, thus predisposing breast cells to cancer formation. The team will explore the mechanisms that link metabolism to heritable breast cancer. They hope to then target metabolic activity in a PTEN-dependent manner with repurposed drugs.

Alternatively, mutations in a gene called KLLN counteract the cancer risk caused by mutations in the PTEN gene. KLLN protects the genome and regulates DNA damage-mediated cell death in breast cancers. This year, the team will further explore this relationship.

This work will allow gene-informed personalization of cancer care from molecular diagnosis, genetic counseling, precise cancer risk assessment, and management of prevention/preemptive strikes.


Charis Eng, MD, PhD is the founding Chair of the Genomic Medicine Institute at the Cleveland Clinic, founding Director of the institute’s clinical component, the Center for Personalized Genetic Healthcare, and Professor and Vice Chairman of the Department of Genetics and Genome Sciences at Case Western Reserve University School of Medicine. She was honored with the Hardis Endowed Chair in Cancer Genomic Medicine in 2008 and the American Cancer Society Clinical Research Professorship in 2009. In 2011, she was elected to the Institute of Medicine of the US National Academies of Sciences for her achievements and leadership in genetics- and genomics-based research and personalized healthcare. Her research has been acknowledged as the paradigm for performing cancer genetics research which can be brought to clinical practice. At the clinical interface, she is acknowledged as one of the rare "go to" people on what is and how to implement genetic- and genomics-enabled personalized healthcare.

Grid Researcher Headshot - Eng C

BCRF Investigator Since


Donor Recognition

The von Mandl Family Foundation Award