September 2011

The CAP has 30 official liaisons to various organizations who attend scientific meetings or designate others to do so. They report to the Standards Committee, which reports to the Council on Scientific Affairs. We publish periodically bits of what the CAP’s outbound liaisons hear and see in their liaison roles.

Embracing the future of genomic medicine

Jason Y. Park, MD, PhD
Jeffrey A. Kant, MD, PhD
Jay F. Schamberg, MD

This year’s annual meeting of the American College of Medical Genetics had genomic medicine and clinical whole genome sequencing as its major themes. Some presentations were about technology guidelines and projects that will ease the transition of genomic technology into the clinical laboratory. What stands out from the meeting is the professional diversity of the attendees working to translate genetic research and technology into health care practice: pathologists, medical geneticists, pediatricians, obstetricians, genetic counselors, and laboratory technicians. CAP member Wayne Grody, MD, PhD, a molecular pathologist and clinical geneticist, is president of the ACMG. This year’s meeting in Vancouver, British Columbia was a 20th anniversary celebration for the ACMG.

Cytogenomics. There were presentations on clinical applications for microarrays determining copy number variants in constitutional diseases as well as oncology. Microarrays have become a dominant clinical platform for the testing of constitutional diseases, and now they are being applied to clinical cancer cytogenetics. Jill Hagenkord, MD, chief medical officer of iKaryos Diagnostics and medical director of molecular pathology and clinical genomics laboratories at Creighton University, gave a presentation on the use of microarrays for high-resolution karyotypic analysis of tumors. Dr. Hagenkord is on the steering committee of the Cancer Cytogenomic Microarray Consortium, which was formed in 2009 and is composed of molecular pathologists, clinical cytogeneticists, and molecular geneticists interested in using microarrays for cancer research and cancer diagnostics (www.urmc.rochester.edu/ccmc/). The consortium is collecting array profiles from various tumors to construct diagnostic algorithms and practice guidelines. One of its goals is to create standards for microarrays to facilitate their use in diagnosing cancers. An ACMG cytogenetics workgroup is drafting guidelines for quality assurance of, and interpreting and reporting, oncology microarray results.

Whole genome sequencing. Advances in DNA sequencing technology have made it feasible, though still expensive, to routinely sequence whole human genomes. The continuing rapid reduction in the price of sequencing opens the possibility within the next decade of $250 genomes in less than an hour. With such advances, WGS is being proposed as a “universal diagnostic” with broad applications in oncology. Mark Boguski, MD, PhD, of the Department of Pathology at Beth Israel Deaconess Medical Center, discussed WGS and the future role pathologists can play, and perhaps must play, given the limited numbers of medical geneticists and counselors.

Clinically significant genetic variation. As laboratories become more capable of sequencing whole human genomes, the focus on determining which genetic changes are clinically significant will intensify. Heidi Rehm, PhD, associate director of the Harvard Medical School Center for Hereditary Deafness, instructor of pathology, and associate molecular geneticist at Harvard Partners Center for Genetics and Genomics, spoke of the need for consistency in mutation databases. Most databases of genetic variation are now research-based, nonstandardized, and not curated. The quality of the information in them is therefore highly variable. Many clinical genetics laboratories compile their own private databases on disorders they test in high volume; traditionally these databases are not publicly accessible. Dr. Rehm discussed the need for a large sequencing project of 2,000 control patients to determine if sequence variants are novel. Finally, she described a future model for clinical genetic reports that integrates DNA sequence results with the patient’s phenotype.

NIH Genetic Test Registry. In its first phase, the registry (oba.od.nih.gov/GTR/gtr_intro.html) is focusing on Mendelian disorders; later it will include pharmacogenetic assays and then multiple gene panels. The registry will have links to references and resources and 24 required data fields and 90 optional data elements. The aim is for it to be a consumer-friendly directory of genetic tests that also includes information on analytical and clinical validation and clinical utility. It should be available by the end of this year.