SC2: Development and Implementation of NGS Diagnostics for Precision Medicine

SUNDAY, MARCH 1 | 2:00 - 5:00 PM

ABOUT THIS COURSE:

Leading precision medicine applications of NGS-based diagnostics have focused on the detection of germline and somatic variants in blood and tissue samples. This short course will present principles and examples of the processes followed in the development, validation, and implementation of NGS-based diagnostics for two clinical scenarios. These will include exome sequencing for the identification of causative germline variants in patients with undiagnosed disorders, and multi-gene panel sequencing for the detection of somatic variants relevant to diagnosis, prognosis, and therapy of tumors. These examples will be complemented by a discussion of key laboratory implementation considerations to assure compliance with regulatory oversight.

TOPICS TO BE COVERED:

• Contrast the advantages and limitations of DNA and RNA sequencing for detection of gene rearrangements
• Relate the principles underlying use of tumor mutation burden and microsatellite instability for prediction of response to cancer immunotherapy
• Recent developments in CAP accreditation and proficiency testing
• CLIA certification, CLSI standards development, and legislative efforts relevant to FDA oversight of laboratory-developed testing employing NGS

COURSE AGENDA:

2:00 pm Evolving Regulatory Landscape for Next-Generation Sequencing Based Diagnostics

Karl V. Voelkerding, MD, Professor, Pathology, University of Utah; Medical Director for Genomics and Bioinformatics, ARUP Laboratories

Published guidelines for validation of next-generation sequencing (NGS) based diagnostic assays have provided clinical laboratories with expert consensus-developed recommendations for both germline and somatic variant testing. Inclusive in these recommendations are guidance on numbers and types of samples for validation, test design, statistical approaches for data evaluation, and recommended quality metrics to implement and monitor. Evolving activity in regulatory oversight of NGS-based diagnostic assays at the organizational standards, accreditation, and federal levels is ongoing. This presentation will provide an update of these ongoing activities with a focus on recent developments in CAP accreditation and proficiency testing, CLIA certification, CLSI standards development, and legislative efforts relevant to FDA oversight of laboratory-developed testing employing NGS.

2:55 Combined DNA and RNA Sequencing for Targeted and Immuno-Oncologic Therapy Selection

Joshua Coleman, MD, Assistant Professor, Pathology, University of Utah, Medical Director for Molecular Oncology, ARUP Laboratories

Next-generation sequencing has been a standard methodology of clinical laboratory practice for the better part of a decade now. Although DNA has been the primary target so far, combined approaches with RNA sequencing are becoming more popular for concomitant detection of gene rearrangements and splicing variants. Increasingly, comprehensive oncology panel designs also include assessment of tumor mutation burden and microsatellite instability. These and other uses of next-generation sequencing will be addressed in this talk, with relevant examples from the field of oncology, both for selection of targeted inhibitors and immunotherapies.

3:50 Session Break

4:05 Adopting Genome Sequencing as a Backbone for Germline Molecular Tests

Jillian Buchan, PhD, Clinical Assistant Professor, Pathology, Stanford University

Targeted enrichment methodologies provide a standard approach for clinical laboratories to perform next generation sequencing (NGS) on a fraction of the genome at markedly reduced costs. However, as NGS costs decline, the need to limit sequencing to only specific genes evaluated by the test will be minimized. This has emerged in recent years as clinical laboratories have begun offering gene panel tests interpreted from data generated by exome enrichment (exome-backbone panels) but expanding this approach to a genome-backbone provides further benefits. This presentation will provide an overview of the use of PCR-free genome sequencing as a backbone for clinical exome sequencing and gene panel testing and how this transition might improve laboratory operational workflows, minimize efforts for test development and validation, and enhance interpretive abilities of tests.

5:00 Course Ends

INSTRUCTORS:

Karl V. Voelkerding, MD, Professor, Pathology, University of Utah; Medical Director for Genomics and Bioinformatics, ARUP Laboratories

Karl V. Voelkerding, MD, FCAP, received his Medical Degree from the University of Cincinnati College of Medicine in 1983. Subsequently, he completed postdoctoral research and clinical training in molecular biology and clinical pathology. In 1990, he joined the faculty of the Department of Pathology and Laboratory Medicine at the University of Wisconsin in Madison, Wisconsin, where he developed and directed a molecular diagnostics laboratory while also practicing transfusion medicine. In 2001, Dr. Voelkerding served as President of the Association for Molecular Pathology, and in 2002 he moved to Salt Lake City, Utah to join the ARUP Laboratories. Currently, he is a Professor of Pathology at the University of Utah and a Medical Director of Genomics and Bioinformatics at the ARUP Laboratories. Dr. Voelkerding has a longstanding involvement in the translation of new technologies into molecular diagnostics, and this interest has focused over the past several years on next generation sequencing. He is currently the Chair of the College of American Pathologists Genomic Medicine Resource Committee.

Joshua Coleman, MD, Assistant Professor, Pathology, University of Utah, Medical Director for Molecular Oncology, ARUP Laboratories

Dr. Coleman is an assistant professor of pathology at the University of Utah School of Medicine and director of genomics for the Division of Anatomic Pathology at ARUP Laboratories. He earned his MD at Case Western Reserve University School of Medicine in Cleveland, OH, in 2007. Dr. Coleman subsequently completed his residency in anatomic and clinical pathology at the Cleveland Clinic (2011), followed by fellowships in hematopathology at the University of New Mexico (2012) and molecular genetic pathology at ARUP Laboratories/University of Utah (2013). He is board-certified in molecular genetic pathology, hematopathology, and anatomic and clinical pathology, practicing most recently at the Ohio State University (2013-16). Immediately prior to joining the University of Utah, Dr. Coleman served as the vice president of medical affairs with GenomOnocology, LLC, in Cleveland, Ohio. His academic interests include leveraging machine learning techniques to facilitate interpretation of genomic data.

Jillian Buchan, PhD, Clinical Assistant Professor, Pathology, Stanford University

Jillian is a board-certified Clinical Molecular Geneticist working in Stanford Medicine’s Clinical Genomics Program (CGP). She completed a research-based MS at University College Dublin in Ireland and later received her PhD in Molecular Genetics and Genomics in 2014 from Washington University in St. Louis. After her PhD, Jillian joined Harvard Medical School's Genetics Training Program and completed her fellowship in Clinical Molecular Genetics in 2016. Jillian then joined the Department of Pathology at Stanford School of Medicine and became board-certified by the American Board of Medical Genetics and Genomics in 2017. Her focus is on molecular-based diagnostic testing, with the majority of her time spent in the CGP, where she oversees overall laboratory operations, development of new next-generation sequencing-based clinical assays, ensures CAP/CLIA regulatory compliance, and signs out clinical test reports. She and her team launched Stanford's first clinical exome sequencing test, and the first test for the newly created CGP, in early 2018.

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