Genomic Medicine Institute News: 2011

December 2011 recently listed their picks for top 50 Physicians who made amazing contributions to medicine and to Cleveland Clinic, and whose names are forever tied to the renowned health system. GMI's very own Charis Eng, MD, PhD, Hardis/ACS Professor and Founding Chair of the Genomic Medicine Institute of Lerner Research Institute falls at an impressive 31. Read more here

web Click here to download the current issue of Translations, the newsletter of the Genomic Medicine Institute. In this issue you will find:
  • IN THE CLINIC: Family History, tried and true
  • UNDER THE SCOPE: Angela Ting, PhD studies changes in DNA methylation that may account for differences in the aggressiveness of prostate cancer
  • GENETICS EDUCATION A new ODH grant will support the CPGH’s designated “Regional Comprehensive Genetic Center”


October 27-30, 2011

CPGH genetic counselors made a splash at this year’s National Society of Genetic Counselors Annual Education Conference, held in San Diego, CA October 27-30, 2011. The Presidential Address of the in-coming Society president Brenda Finucane highlighted “a whole group of genetic counselors at the Cleveland Clinic’s Genomic Medicine Institute” for innovative clinical practice, the breadth of practice, research, utilizing IT and positive energy. CPGH genetic counselors garnered a record number of presentations, including a plenary presentation, 5 proferred platform presentations, 4 poster presentations and an educational session.

Plenary Presentations

Jessica Mester – “Comparison of Genetic Counselor Time Investment Utilizing Coupled and Uncoupled Practice Models: Final Results from the Cleveland Clinic General Genetics Clinic Time Study” – Best Abstract Award Recipient

Oral Abstract Presentations
Amy Shealy – “Novel Microduplication of 12q13.12 Including TUBA1A and DHH Detected in a Boy with Abnormal Brain MRI Findings, Cryptorchidism, Urethral Stricture and Pubertal Delay”

Marissa Smith – “Expanding Genetic Counseling Services to an Executive Health Program: Identifying Risk for Genetic Disease in a Low-Risk Population”

Jessi Moline – “Approach to Systematic Screening of Endometrial Cancers for Lynch Syndrome: the Cleveland Clinic Experience”

Brandie Leach – “A Time Study of Genetic Counselor Only versus Traditional Care Genetic Counselor/Geneticist Patient Care in a Cancer Genetics Setting”

Jill Polk
– “Ethico-legal Obligations in Hereditary Diffuse Gastric Cancer Kindred with Novel CDH1 Mutation”

Poster Presentations
Allison Schreiber – “CHD7 Variants in Two Families with Evidence of Parent-to-Child Transmission of CHARGE Syndrome”

Patty Arscott
– “Genetic Counseling Dilemma: Multiple Gene Variants Identified Through Genetic Testing for Hypertrophic Cardiomyopathy”

Christina Rigelsky – “Clinical Features of Three Patients with Vascular Ehlers-Danlos Syndrome as the Result of COL3A1 Functional Haploinsufficiency with Stable mRNA but Unstable Protein”

Rebecca Cook – “Assessing the Utility of Four Educational Videos Concerning Alpha-1 Antitrypsin Deficiency” and “Guidelines for Advocacy Organizations Considering Establishing a Registry or Biobank”
Educational Breakout Session Presentations

Meg Doerr – “Using Information Technology to Facilitate the Cancer Genetic Counseling Process”

October 11, 2011

Dr. Eng named one of US News and World Reports’ Top Doctors

Charis Eng, MD, PhD, FACP, Hardis and ACS Professor, founding Chair of the Genomic Medicine Institute and Director of its clinical component, the Center for Personalized Genetic Healthcare, was honored by being named one of US News and World Reports’ Top Doctors.  The US News and World Report – Health – evaluates physicians and surgeons in the nation for top doctors in 75 subspecialties, with 28,000 standing top doctors.  Dr. Eng was cited for being a top doctor in medical oncology and clinical cancer genetics.

Dr. Eng delivers Herrera Lecture on Genomics-Based Personalized Healthcare

Charis Eng, MD, PhD, FACP, Hardis and ACS Professor, founding Chair of the Genomic Medicine Institute and Director of its Center for Personalized Genetic Healthcare, was honored for her distinguished contributions to cancer genetics by delivering the Herrera Lecture at the 15th Annual Meeting of the Collaborative Group of the Americas on Inherited Colorectal Cancer, Montreal, Canada, October 11-12, 2011.  This CME-accredited meeting attracts hundreds of registrants from around the world.  The late Dr. Lemuel Herrera was a surgical oncologist whose astute clinical observation led him to team up with distinguished geneticist Dr. Avery Sandberg at Roswell Park Cancer Institute to find the APC gene, associated with familial adenomatous polyposis, the first described heritable colorectal cancer syndrome.  Dr. Eng presented this year’s Herrera Lecture on “Genetics and Genomics-Based Personalized Healthcare: Something Old, Something New” where she gave a historical perspective of personalized medicine, and then detailed the last 6-years’ experience of the Genomic Medicine Institute leading, participating or coordinating efforts for successful integration of genetics processes and clinical genetic services throughout the Cleveland Clinic Health System in order to increase access to genetics-based personalized healthcare.  She then outlined the expected and unexpected challenges facing the breath of personalization of health care delivery going forward. 

July 27, 2011

Dr. Eng and team discover new genetic link to Barrett esophagus, esophageal adenocarcinoma

The Eng Lab, collaborating with the Meltzer Lab at Johns Hopkins Medical Institutions, have identified genetic mutations in patients with Barrett esophagus (BE) and/or the esophageal adenocarcinoma (EAC). None of these mutations were found in patients not affected by BE/EAC, suggesting a previously unknown heritable cause. Identifying genetic markers will allow risk assessment, early detection, improved disease management, and ultimately increased survival.

BE is estimated to occur in up to 10 percent of the population, and its incidence has increased more than three-fold since 1970. Related to gastroesophageal reflux disease (GERD), BE is believed to be a precursor to EAC. EAC is typically not diagnosed until its advanced stages, when chances of survival are poor.

This study, published in the July 27, 2011 issue of the Journal of the American Medical Association and led by Charis Eng, MD, PhD, Hardis/ACS Professor and Founding Chair of the Genomic Medicine Institute of Lerner Research Institute at Cleveland Clinic, was conducted from 2005 to 2010 at 16 different institutions across the United States and involved 298 white participants with BE, EAC, or both.

To identify genes linked specifically to BE/EAC, the group used the latest in integrative genomics approaches and state-of-the art technology, along with functional genomic validation, to identify MSR1, ASCC1, and CTHRC1 as three genes mutated in 11 percent of the BE/EAC patients studied, indicative of a significant genetic predisposition. Mutations in MSR1 were the most common, affecting seven percent of the patients studied.

Identifying BE/EAC predisposition genes also gives valuable insight to how the disease occurs. Preliminary evidence from this study suggests a role for specific molecular pathways, including inflammation, in the development of BE/EAC, as well as a potential link of the mutated genes to additional cancers as well.

“We are absolutely thrilled to now know three distinct genes that link to BE/EAC,” said Dr. Eng. “This is essential for improving risk assessment, disease management, and saving lives.”

Other authors include members of the Eng Lab, Drs. Mohammed Orloff and Xin Jason He, Charissa Peterson, Shireen Ganapathi and Todd Romigh; and the genetic counselor coordinator of the Barrett’s protocol, Brandie Heald Leach, MS, CGC.

July 24-28, 2011

Dr. Eng presents at an invited symposium on direct-to-consumer genomic testing at the Annual Meeting of the American Association of Clinical Chemistry, Atlanta, GA

Charis Eng, MD, PhD, FACP, Hardis and ACS Professor, founding Chair of the Genomic Medicine Institute and Director of its Center for Personalized Genetic Healthcare, presented at AACC Morning Symposium on Direct-to-Consumer Genomic Testing: Opening Pandora’s Box chaired by KT Jerry Yeo, PhD from the University of Chicago. Dr. Eng presented the “Bioethical and Clinical Dilemmas of Direct-to-Consumer Genomic Testing”; and Dr. Jeff Gulcher, MD, PhD, CMO of DeCode Genetics, presented “Genetic Risk Tests for Common Diseases: for Physician Eyes Only?” After the talks, a lively scholarly panel discussion ensued.

June 29, 2011

Dr. Eng presents at the NIH’s Genomic Medicine Institutes’ Leaders Colloquium, Chicago, IL

Charis Eng, MD, PhD, FACP, Hardis and ACS Professor and founding Chair of the Genomic Medicine Institute and Director of its Center for Personalized Genetic Healthcare, took a one-day break from her vacation to present at a by-invitation-only Colloquium of Leaders of Genomic Medicine Institutes hosted by NHGRI and the NIH. The goal of this day-long Colloquium is to do an as-is assessment on and discuss opportunities, challenges and solutions to integrating genetic and genomic processes and services into routine clinical care. Dr. Eng presented how the Genomic Medicine Institute collaborated with the Digestive Disease Institute and Pathology and Lab Medicine Institute to successfully integrate microsatellite testing and mismatch repair protein immunohistochemistry into pathology routine for all colorectal carcinomas resected on Cleveland Clinic main campus. This has led to an uptake of 80% of test-positive individuals reaching GMI’s Center for Personalized Genetic Healthcare, and an effective strategy for identifying the majority of adult-onset heritable colon cancer (Lynch syndrome).

May 24-25, 2011

Dr. Eng delivers plenary lecture at 2011 Healthsmart Forum on reform legislation and the future of integrated self-funded healthcare
Charis Eng, MD, PhD, FACP
, Hardis/ACS Professor and Chair of the Genomic Medicine Institute and Director of its Center for Personalized Genetic Healthcare, delivered a plenary lecture about genetics and genomics-enabled disease risk assessment, prediction and tailored medical management. She provided compelling evidence that this type of strategy will ensure value-based delivery of healthcare for the 21st century.

April 28th, 2011

Charis Eng, MD, PhD, one of 40 invited leaders to a meeting of the Personalized Health Project in San Francisco
The tools for personalizing healthcare are extremely promising but as with anything new, there are multiple conceptual and practical barriers. This meeting convened by David Ewing Duncan, is a “take action” summit of leaders in the personalized health space including prominent leaders from science, IT, business, government, media, patient advocacy, etc. Charis Eng, MD, PhD, FACP, Hardis/ACS Professor and Chair of the Genomic Medicine Institute and Director of its Center for Personalized Genetic Healthcare, was one among 36 personalized health leader panelists, and she addressed “Personalized Healthcare: Clinical Challenges (and Opportunities)” Video can be seen here.

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Dr Eng and Dr. Stephen P. Spielberg, MD, PhD, Director, Center for Personalized Medicine and Therapeutic Innovation Children’s Mercy Hospital, Kansas City; former Dean, Dartmouth Medical School Dr Eng and David Ewing Duncan, Journalist and Director, Center for Life Science Policy, University of California, Berkeley Dr Kathryn Teng, Director Center for Personalized Healthcare and Dr Eng


April 14th, 2011

2010 State of the Genomic Medicine Institute Address
Charis Eng, M.D., Ph.D. presented the State of the GMI to the department, their adjunct faculty, members of LRI and CCF, and members of the GMI's External Advisory Board. The presentation highlighted GMI's accomplishments of 2010 and the goals for 2011. The presentation is available for download here (PDF file).

March 25th-26th , 2011

Dr. Eng is a distinguished speaker at 3rd Annual Forum for Payers of Personalized Medicine, Washington, DC
Charis Eng, MD, PhD, FACP
, Hardis/ACS Professor and Chair of the Genomic Medicine Institute and Director of its Center for Personalized Genetic Healthcare, delivered a plenary lectures at PWC’s Center for Business Intelligence forum. She detailed evidence for genetics and genomic medicine-enabled personalized healthcare by describing some of the Genomic Medicine Institute’s successes in integrating genetics and genomic medicine services into main campus specialty clinics, family health centers and regional community hospitals of the Cleveland Clinic Health System over the last 5 years. She also discussed the challenges and barriers to personalized healthcare delivery and its attendant clinical and research opportunities.

March 2 , 2011

Charis Eng, MD, PhD delivers State-of-the-Art Keynote lecture on genetics-informed personalized healthcare in Phoenix
At the Winter Meeting of the Society of Urodynamics and Female Urology, Phoenix, AZ, Charis Eng, MD, PhD, FACP, Hardis Chair of the Genomic Medicine Institute and Director of its Center for Personalized Genetic Healthcare delivered Keynote lecture entitled, “Genomic medicine for personalizing 21st century patient care.” She described the rationale for genomic medicine as a strong platform for delivering value-based health care in the context of causes of death and illness and of health industry’s top issues. She called attention to the breath of personalized patient care to range from meticulous documentation of clinical information to gene-based risk assessment to gene-informed personalization of increased clinical screening, behavior modification and/or choice of therapy. She gave one example of how her genetics and genomic medicine research has been translated to personalizing cancer patient care, and described what the Cleveland Clinic is doing in leading the charge in personalizing healthcare. Finally, Eng described new genomics advances including whole genome sequencing for potential clinical application with its opportunity for changing the paradigm of healthcare and its multiple attendant challenges. While the main focus of this Society is not related to cancer genomic medicine, the conveners of the meeting had hoped that this invited keynote from a completely different field would guide and inspire their members into thinking of their own research that will one day personalize patient care in their specialty.

February 21 , 2011

GMI stars in National Geographic TV Special “Lincoln’s Secret Killer” which premiered on President’s Day, 2011
"Lincoln's Secret Killer," a documentary prepared by National Geographic, premiered on Monday, February 21, at 10:00 pm on The National Geographic Channel, featuring Charis Eng, MD, PhD, Hardis Chair, Genomic Medicine Institute and GMI’s Director of the Center for Personalized Genetic Healthcare, and members of her lab, Mohammed S. Orloff, PhD, Project Scientist, and Todd Romigh, MS, Lab Manager.

Popular knowledge says Lincoln had Marfan syndrome, yet, he did not have the sentinel features. Indeed, the National Geographic asks, “Was Lincoln dying of cancer when he was killed?” A trained cardiologist and obscure diagnosis expert of historical figures John Sotos, MD believes that Lincoln and three of his four sons suffered from MEN 2B, a rare, inherited cancer syndrome. When Sotos first brought his hypothesis to Eng in 2007, she was one of the few cancer geneticists who felt this was plausible and asked for molecular proof. The investigation traces the path of Lincoln's assassination blood trail, searching for historical relics stained with Lincoln's blood. At Cleveland Clinic's Genomic Medicine Institute, Dr. Eng oversees the first round of DNA testing – from a dress swatch said to be stained with Lincoln's blood. Meanwhile, in an ancient DNA lab in New Zealand, Dr. K. Ann Horsburgh also tries to crack the code. It is the first-ever attempt at testing Lincoln's DNA, but it's no easy task. Sotos believes a whole new chapter in Lincoln history still waits to be written."

Dr. Sotos' hypothesis is that Lincoln had MEN 2B (a type of multiple endocrine neoplasia (MEN) caused by RET mutations) instead of Marfan syndrome, which has been postulated in the past. Although a genetic condition distinct from Marfan syndrome, MEN 2B is characterized by marfanoid habitus, a term that describes the co-occurrence of many Marfan syndrome features. Dr. Eng, who identified the MEN 2B allele while a postdoctoral fellow in Prof. Sir Bruce Ponder's laboratory at the University of Cambridge, UK and who currently leads the International RET Mutation Consortium, was the cancer genetics consultant for Dr. Sotos' hypothesis. The Eng laboratory team worked on extracting DNA (with which to assay for RET mutations using polymerase chain reaction (PCR)) from clothing stained with Lincoln's blood. The documentary was 13 months in the making.

A mock genetics evaluation and genetic counseling session with Dr. Eng, Brandie Leach, MS, CGC and Jessica Moline, MS, CGC of an MEN 2B family was originally filmed but not included in the televised segment. The genetic evaluation and counseling session are very important because with the discovery of the risk gene and associated clinical features of MEN 2B (and the other MEN 2 variants), accurate molecular diagnosis and predictive gene testing can result in prevention of the MEN 2-related cancers. In other words, if President Lincoln carried the MEN2B gene and lived today, he would have been pre-emptively diagnosed and the related cancers could be prevented or caught early.

January 7, 2011

labDr. Eng and team create scoring system to facilitate identifying individuals to be referred to PTEN gene testing
Researchers have discovered a method for more precise identification of individuals who should undergo testing for genetic mutations of the tumor suppressor gene PTEN, which associates with a variety of conditions including several types of cancers. The research has created a diagnostic scoring system that improves on established criteria.

Led by Charis Eng, M.D., Ph.D., Hardis Chair of the Genomic Medicine Institute and Director of its Center for Personalized Genetic Healthcare of Cleveland Clinic, the study – the largest clinical study to date on the identification of PTEN – involved 3,042 participants, including both adults and children. Dr. Eng and her team established a semi-quantitative diagnostic score as an evidence-based improvement over the existing National Comprehensive Cancer Network (NCCN) 2010 diagnostic criteria, resulting in more accurate diagnoses and, theoretically, better outcomes.

These results contribute to clinical practice recommendations. “The new criteria give non-genetics healthcare providers a guide of who should be referred to genetics evaluation, which includes genetic counseling,” said Dr. Eng. “Knowing one’s PTEN gene status will lead to personalized cancer screening, resulting in catching cancers earlier or even preventing them from coming at all.”

In addition to the association between mutant PTEN and disease, the study’s novel scoring system also incorporates the amount of PTEN protein as it relates to disease. A higher diagnostic score correlates with lower PTEN protein, substantiating previous laboratory studies that show lower PTEN levels associate with carcinogenesis. “This is the first human evidence of a causal relationship between PTEN protein deficiency and disease manifestation, which had only been previously been shown in the laboratory dish or animal model,” Eng remarked.

For the first time, the scoring system provides criteria for addressing important differences in assessing pediatric versus adult patients. Furthermore, autism, which was first linked to mutant PTEN by Dr. Eng and her team, is included in the clinical criteria. Although vascular malformations (altered blood vessels) have long been reported in adults with Cowden syndrome, the malformations are not part of NCCN criteria. In contrast, the newly discovered criteria specifically recommend these patients undergo further genetic testing for early diagnosis of other lurking complications, such as cancers, so that more careful screening can occur.

Other authors include members of the Eng lab, Drs. Min-Han Tan (who is first author) and Mohammed S. Orloff, Charissa Peterson, Jin-Lian Chen and Yiran Yang; genetic counselor coordinator of the PTEN study Jessi Mester, MS, CGC; biostatistician Lisa A. Rybicki; and members of the multidisciplinary PTEN team, thyroid specialist and surgeon Dr. Mira Milas, who is also Director of Cleveland Clinic’s Thyroid Cancer Center; breast specialist Dr. Holly Pederson; and dermatologist Dr. Berna Remzi. The PTEN risk calculator is now available at the GMI website.