I was reading about the FDA’s recent crackdown on 23andme to stop marketing their saliva based whole genome testing and interpretation service. Rather than resist, 23andme decided to comply and is currently in “talks” with the FDA so that they can complete the process for FDA validation and again begin to market their kits and testing. For now, they can continue to provide their genealogy testing and whole genome sequencing without interpretations.
Currently, in some academic research centers, whole genome or exome sequencing via next generation sequencing (NGS) methods is utilized on a limited basis by researchers and clinicians to identify pathogenic mutations. NGS and bioinformatic analysis methods continue to steadily improve and costs have been decreasing. However, there are limitations and barriers to widespread use at this point. These include but are not limited to: 1) widely used databases such as the Human Gene Mutation Database (HGMD) and the Online Mendelian Inheritance in Man (OMIM) still only contain information that only covers a fraction of the human genome, 2) more research is still needed to identify more variants mutation-disease associations, and 3) most mutations identified fall under the category of “unknown clinical significance”.
Tools such as NGS, despite its improvement over previous technology, still cannot identify large deletions or copy number variations (CNV) and is a technology not accessible, cost-wise and support-wise, to most health care institutions. Despite all of this, primary care physicians, even now, still may be confronted with patients who bring them their genomic screening results, whether obtained from commercial services provided by companies like 23andme or through molecular testing through a health care institution. But today’s physicians, including primary care physicians and pathologists, were not trained in medical school to understand how this testing is performed or the significance of these results. But the time is coming, and maybe sooner than we realize, when we will have to deal with such testing on a daily basis.
So, it is imperative that we train our doctors and doctors-in-training now to be ready for when that time comes. But, my question this week is “How should we go about it?” Additionally, who should compose the health care team to provide guidance and counseling to patients once results are available? And who should regulate how testing should be done and what information should be included in results reporting? Leave me a comment if you have an opinion or any ideas.
–Betty Chung, DO, MPH, MA is a second year resident physician at the University of Illinois Hospital and Health Sciences System in Chicago, IL.
I wanted to devote this blog to my experience at the recent Training Residents in Genomics (TRIG) one-day workshop at the ASCP Annual Meeting in Chicago. I admit that I am biased since I had ten years molecular and cell biology and transgenics research experience prior to medical school and enjoy all things molecular. But I really I do think that TRIG is an idea whose time has come.
TRIG is a group of molecular pathologists, medical educators, and geneticists who came together in 2010 with the goal to create a standardized, high quality genomics curriculum and to promote adoption at >90% of pathology residency programs by the end of their 5-year grant period. A 2010 survey of 42 pathology residency program directors found that only 93% confirmed molecular pathology as a part of their training and only 31% had established curricula on relevant topics. So, TRIG plans to provide online resources, lectures and workshops, and to assess the efficacy of genomic medicine curricula at residency programs through RISE performance. From speaking to other residents I’ve met over the past year, I know that the teaching of molecular pathology at each program can vary significantly.
The TRIG workshop had four sessions that followed the case of a woman with newly diagnosed breast cancer while applying specific hands-on skills related to the genomic related elements of her case. I missed the first session so I can’t say too much except that they discussed single gene testing and assessment of BRCA mutations of unknown clinical significance. Session two covered the assessment of prognostic gene panels (Oncotype DX) and compared them versus the standard breast IHC panel. We also learned to plot Kaplan-Meier survival curves based on a patient’s genomic profile on a publicly available website.
After lunch, session three dealt with the selection of genes to design a breast cancer multi-gene assay for this patient. Questions considered were the availability of targeted drug therapy for specific somatic mutations, the strength of association of selected genes with breast cancer, frequency of these variants, reimbursement, and choice of PCR based genotyping versus next-gen sequencing. The final session focused on the creation of a genomic pathology report for this patient after analyzing the clinical significance of each result from multi-gene mutational analysis using free web-based tools.
This workshop was a great introduction for the genomics neophyte (especially if one’s residency is weak in this subject or doesn’t have a molecular pathology rotation) and even someone with some experience like myself, learned how to use some new tools and applications even though the concepts were not new to me. As I mentioned in previous blogs, I learn more from having to tackle issues hands-on and being able to participate in a bidirectional discussion about a topic versus reading textbooks or attending lectures. The workshop was a good intro albeit too short to learn to apply these skills comfortably and effectively…but it is definitely a step in the right direction and I expect to see more great things coming out of the TRIG Working Group. More info about TRIG is at www.ascp.org/trig.