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NGS Leaders Blog

CAP and the Clinical Application of Genetics

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Editor’s Note: We are pleased to share an article submitted by Nazneen Aziz. Nazneen is the Director, Molecular Medicine, in the Transformation Program Office at the College of American Pathologists. Email: Naziz@cap.org 

azizSeptember 6, 2012 :
Nazneen Aziz : 
This is an interesting time to be a geneticist. With the whirlwind of recent activities ongoing in the adoption of next generation sequencing (NGS) in diagnostic medicine, I am glad I am one. I never regretted choosing to be a molecular geneticist, but the role genetics would play in medicine was not always clear. In the 1980s, when I was a graduate student at MIT, working on translational regulation of ferritin mRNAs, there was tremendous optimism for what molecular genetics could do for medicine – an almost irrational hope that disease-causative genes would be discovered and lead to gene therapy and cure.

Later, while a postdoc at the Whitehead Institute, I felt the whirlwind of excitement at the beginnings of the Human Genome Project and the imminent discovery of 20,000 potential drug targets. The early 2000s saw the birth of many biotechnology companies focused on genetics research and genotyping technologies, only for the unfortunate, perhaps inevitable collapse of many of these companies around 2003-2005.

This was a few years after I had left the Harvard Medical School faculty to join the biotechnology industry. This was not a rosy time to be a geneticist doing human genetics applied research in the biotechnology sector. Geneticists like me began to wonder if we would ever see the true potential of human genetics being applied in clinical medicine in our careers - or in our lifetime.

We certainly could not have imagined that, just six years later in 2012, we would see the entire genome of patients being sequenced to diagnose disease! Today, genetics is truly being applied in real time to diagnose otherwise inexplicable diseases. Genomic level sequencing is successfully being applied to end the multitude of diagnostic tests that patients had to endure earlier without revealing the underlying cause of their disease.

Ironically, genomic level sequencing as a clinical test could not have happened were it not for the discovery of NGS technologies – a technology that matured around 2005, just as many pioneering genomics firms were collapsing.

Rapid Adoption  

No other technology has seen clinical adoption so rapidly. Diagnostic labs are either already offering or gearing up to offer clinical tests that consist of gene panels, exome or genome. All of this is possible because NGS has dropped the costs of clinical sequencing dramatically, even beating Moore’s Law. Another important factor is also the availability of table-top and less costly sequencing machines.

With clinical large-scale genomic sequencing comes a multitude of questions and needs:
· What standards will the diagnostic labs apply for these highly complex tests?
· Will insurance companies pay for the tests?
· How do we get patient consent for this complex test that can reveal so much more than the specific condition the patient is tested for?
· How do clinicians report incidental findings (significant but unexpected findings)?
· How do clinicians and laboratory technicians interpret new variants that appear to be pathogenic but have never been reported before?
· And what databases do we refer to in order to create the test reports?

At the College of American Pathologists (CAP), which has a long history of developing gold standards for clinical laboratories and is an accrediting body for CLIA, many of these questions are being considered, debated and discussed vigorously. I lead a new committee formed at CAP called the Next Generation Sequencing Work Group (NGS WG), which consists of about 14 member pathologists, CAP staff and representative members from the Association of Molecular Pathologists and American College of Medical Genetics. CAP thought this rapidly developing technology area to be important enough to convene this group and dive into many of these issues, which have no easy answers, but clearly need solutions developed before next generation sequencing becomes a household name.

As a first step, the NGS WG at CAP developed the first set of standards for clinical laboratories for clinical tests using NGS technologies. This checklist for laboratory standards was recently published and is now available to all. However, the work for the NGS WG is not done, as the checklist needs to be expanded and refined to address areas such as cancer and infectious disease. We also hope to explore the development of proficiency test products that assess an operator’s ability to accurately detect and annotate variants.

The excitement is not just present at CAP; several governmental and professional societies are also developing their own guidelines on the multifaceted needs of NGS tests, which involve ethics, interpretation, reporting, consenting, and billing. This flurry of activity and urgency to deal with the practical aspects of this new test is occurring because, for the first time, the true potential of the clinical applications of genetics has been unleashed.

CAP is excited to be a partner with the many organizations driving the future of genomic medicine, and we welcome any ideas, questions, or issues you may have.

I-Study: Genomic Interpretation - Who Will Pay?
During this webinar, members of the study review team present preliminary findings of the I-Study, conducted at the Harvard Medical School's 2011 Personalized Medicine Conference.
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