Cleveland Clinic researcher identifies 2 new genetic mutations associated with Cowden syndrome

December 13, 2012

Thursday, December 13, 2012, Cleveland: Cleveland Clinic researchers from the Lerner Research Institute have uncovered two new genes associated with Cowden syndrome (CS) according to a new study, published today in the online version of the American Journal of Human Genetics.

Cowden syndrome is a difficult-to-recognize, under-diagnosed condition that carries high risks of breast, thyroid, and other cancers. The discovery of the two new genes - led by Charis Eng, MD, Ph.D., Chair and Founding Director of the Cleveland Clinic's Lerner Research Institute's Genomic Medicine Institute - will promote diagnosis and clinical management of the disease, while also assisting in predictive genetic testing and genetic counseling.

Researchers performed genetic sequencing on DNA from individuals with CS who have none of the known genetic alterations associated with CS. State-of-the-art technology was used to identify a high prevalence of mutations in the PIK3CA and AKT1 genes, which are involved in cancer-related signaling pathways.

In tracing the root causes of CS, Dr. Eng has previously identified many genetic alterations that promote the disease, beginning with mutations in the first gene ever to be associated with CS, the tumor suppressor, PTEN, along with the SDHB/D and KLLN genes, identifying their connection with PTEN in cancer.

"Gene-enabled risk assessment and management begins with the identification of all the genes that, when mutated, account for as many or all the individuals with a particular syndrome, in this case CS," said Dr. Eng. "We started with only PTEN, and now we know that SDHB/D, KLLN, PIK3CA and AKT1 account for CS. Each also brings differing risks of breast, thyroid and other cancers, and so this discovery directly aids genetic counseling and clinical management."

This research comes on the heels of two new discoveries by Dr. Eng, both related to Cowden syndrome and the PTEN gene, that were recently published in the Journal of Clinical Endocrinology & Metabolism.

In a Nov. 1 paper, Dr. Eng and her team reported on uncovered, untapped, diagnostic and prognostic pathways for cancers related to the compromised PTEN tumor suppressor.

This discovery that PTEN disrupts cancer signaling pinpoints a novel target for future treatment and diagnosis. This type of location-specific strategy is important in both heritable and sporadic cancers.

In another paper published Dec. 1, Dr. Eng and her team identified a screening biomarker in thyroid cancers that revealed inherited predisposition in Cowden syndrome patients. With the increasing incidence of thyroid cancer over the last few years, having a biomarker to screen for an inherited mutated PTEN tumor suppressor gene would accelerate follow-up for affected individuals.

After a five-year, multi-center study of patients with Cowden syndrome and Cowden-like syndrome, characterized in part by PTEN mutations, researchers have concluded that a simple blood test may screen for individuals carrying increased cancer risk. Until now, only four clinical factors were known to predict an inherited PTEN mutation - and this study's blood test out-predicts them all. Future studies testing thyroid tissue itself may reveal additional biomarkers.
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Charis Eng, M.D., Ph.D., is Chair and Founding Director of the Cleveland Clinic's Lerner Research Institute's Genomic Medicine Institute, and founding Director of the institute's clinical component, the Center for Personalized Genetic Healthcare. Dr. Eng's research interests may be broadly characterized as clinical cancer genetics translational research. For more information visit: http://www.lerner.ccf.org/gmi/eng/

Research reported in this publication was supported by was funded by the National Cancer Institute of the National Institutes of Health under award number P01CA124570 and R01CA118980, and the Breast Cancer Research Foundation. Dr. Eng holds an American Cancer Society Clinical Research Professorship.

About Cleveland Clinic

Cleveland Clinic is a nonprofit multispecialty academic medical center that integrates clinical and hospital care with research and education. Located in Cleveland, Ohio, it was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. Cleveland Clinic has pioneered many medical breakthroughs, including coronary artery bypass surgery and the first face transplant in the United States. U.S .News & World Report consistently names Cleveland Clinic as one of the nation's best hospitals in its annual "America's Best Hospitals" survey. About 2,800 full-time salaried physicians and researchers and 11,000 nurses represent 120 medical specialties and subspecialties. Cleveland Clinic Health System includes a main campus near downtown Cleveland, eight community hospitals and 18 Family Health Centers in Northeast Ohio, Cleveland Clinic Florida, the Lou Ruvo Center for Brain Health in Las Vegas, Cleveland Clinic Canada, and opening in 2013, Cleveland Clinic Abu Dhabi. In 2010, there were 4 million visits throughout the Cleveland Clinic health system and 167,000 hospital admissions. Patients came for treatment from every state and from more than 100 countries. Visit us at www.clevelandclinic.org. Follow us at www.twitter.com/ClevelandClinic.

Editor's Note: Cleveland Clinic News Service is available to provide broadcast-quality interviews and B-roll upon request.

Cleveland Clinic

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