MDNews - Cleveland-Akron-Canton

COVER FEATURE defines genomics as the study of the entire genetic environment, including the interplay and communication between the 30,000 genes in a human cell and their infl uence on susceptibility to cancer and other diseases. "A human is not just one gene. You have to look at the whole environment," says Dr. Eng. "Genomic medicine should take into account the sum total of gene-gene interactions and gene-environment interactions." Dr. Eng has identified four of the ten genes that raise the risk of breast cancer. She and her team are currently working to identify and characterize the genes that cause two heritable cancer syndromes: Cowden syndrome which increases the risk of breast, thyroid and endometrial cancers, and multiple endocrine neoplasia type 2 (MEN 2) which is characterized in part by medullary thyroid cancer and pheochromocytoma (cancer in the adrenal gland). Her discovery of the RET genotype for MEN2 has led to a test for the gene that is now considered to be standard practice. In co-leading an ongoing multinational study, Dr. Eng and her team have also recently determined that 25% of sporadic pheochromocytoma cases are caused by mutations on one of four genes. Known as "Queen of Cowden," Dr. Eng found a second signifi cant cancer pre- disposition gene for Cowden syndrome which was previously known only to be associated with master gene PTEN. Publishing last winter in JAMA, the Eng lab found that epimutation in KLLN which lies next to PTEN also predisposes to multiple cancers and to a higher degree than PTEN. This summer, the Eng labo- ratory at Cleveland Clinic published in JAMA its fi nding on the genetic mutation underlying Barrett's esophagus and/or the cancer esophageal adenocarcinoma. Additional research studies on the role of genomics in sporadic breast and prostate carcinomas and head and neck cancers are ongoing. "So, our work may have broad implications not only for examining the pathogenesis of common cancers, but may reveal novel targets and novel compartments germane for diagnosis, prognosis, therapy and prevention," Dr. Eng has written of her research. Indeed, she is proud to say her work on the genes predisposing to Cowden syndrome and to various endocrine cancers have rapidly been translated into practice and codified in professional practice guidelines as useful molecular diagnostic and risk assessment tools to personalize genetic counseling and risk management. From Bench to Bedside As a translational researcher, Dr. Eng believes the greatest value for research is in its application in human patients. ("I don't care about mice," she quips.) She has worked to integrate genetic services and genetic counselors throughout the Cleveland Clinic system. In fact, genetic counselors now serve in approximately 20 clinical locations associated with 9 different specialties both on and off the main campus. Last year, 3,000 outpatients saw genetic counselors and geneticists, up from 600 in past years. "Cleveland Clinic serves 3.8 million people a year. In the past, it could 10 | Cleveland-Akron-Canton MD NEWS MDNEWS.COM NOVEMBER-DECEMBER 2011 take many months for a patient to get genetic services. We are turning that around by standardizing the practice of genetic testing and counseling and embedding genetic clinical services into non-genetic clinics," Dr. Eng explains. Her ultimate goal is to streamline and integrate genomic medicine processes into every clinical subspecialty in Cleveland Clinic. Towards that goal, in early 2008 Dr. Eng began to work on a web-based patient-entered tool that would be com- patible with electronic medical records. It included a series of point-of-care clinical decision-support tools including one focusing on family history taking (called MyFamilyHealthHistory) for interrogating risk of cancers and the PTEN Cleveland Clinic Score Risk Calculator. Because of the successful utilization of these tools, Cleveland Clinic is funding a scalable family health history software program for the whole enterprise. As the fi eld of genomics plays a grow- ing role in clinical practice, at Cleveland Clinic and beyond, more physician sci- entists are needed. To meet the demand, Dr. Eng founded and directs the Cancer Genomic Medicine Fellowship Training Program at Cleveland Clinic's Genomic Medicine Institute. Her goal is to bring top minds into a fi eld that she believes represents the future of healthcare. "Right now, most clinicians practice by the law of averages," she explains. "We prescribe drugs and see that 15 percent of people respond to it, but what about the other 85 percent? Genomic medicine will allow us to personalize the choice of medications as well." Dr. Eng says she is proud to have led Cleveland Clinic into this new era, and she looks forward to a future in which translational researchers, who are also physicians like her, will play an increas- ingly critical role. "Anyone can do research," she says. "But we need translational investiga- tors to translate that into something meaningful for the patient." n

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