Molecular Oncology: The Role of Next-Generation, Sequencing-Based Gene Panels in Solid Tumors
Somatic mutation testing of various solid tumors has prognostic value and is thus routine in oncology patient care. For several tumor types, multiple genes are pertinent, but reflex testing with single-gene assays can create delays in therapeutic decision-making. With the advent of clinical testing of tumors with next-generation sequencing (NGS) technology, a single comprehensive test can potentially replace multiple individual gene assays and expedite patient care.
NGS provides breadth of sequence coverage beyond the scope of well-characterized mutations, potentially improving the therapeutic options available for patients. However, this improved coverage presents a challenge to interpreting variants and meeting reasonable clinical turnaround times for reporting.
These challenges will be discussed within the context of clinical case examples, with an emphasis on “lessons learned” in the adoption of NGS for solid tumor mutation testing.
Originally Presented on June 25, 2014 in Salt Lake City, Utah
Allie Grossmann, MD, PhD
Staff Pathologist, Surgical Pathology and Oncology, ARUP Laboratories
Instructor of Pathology, University of Utah School of Medicine
Dr. Grossmann is a staff pathologist in the Surgical Pathology and Oncology Division at ARUP and an instructor of pathology at the University of Utah School of Medicine. Dr. Grossmann received a BS in zoology at the College of Idaho and a PhD and MD from the Oregon Health Sciences University, where she studied tyrosine kinase substrate specificity with Brian J. Druker, MD. Dr. Grossmann completed both a residency in anatomic pathology and a research fellowship in molecular medicine at the University of Utah. Her postdoctoral work in the laboratory of Dean Y. Li, MD, PhD, focused on the role of small GTPases in melanoma invasion and metastasis. Most recently, Dr. Grossmann completed a fellowship in molecular genetic pathology at ARUP Laboratories. Her primary subspecialty interests are sarcoma pathology and molecular oncology. Her research interests include mechanisms of tumorgenesis, metastasis, and the development of targeted therapies for cancer treatment.
After this presentation, participants will be able to:
- Describe the advantages and disadvantages of NGS testing in oncology.
- Understand how the choice of validation samples can define the limits of the test, and how this relates to sequence variant interpretation.
- Discuss some of the challenges in interpretation and classification of sequence variants.
- Summarize some of the resources available for help with variant interpretation and classification.
- Consider proposed criteria that may help discern the pathogenicity of variants.
- Review clinical cases that demonstrate the challenges of classifying and interpreting variants.
University of Utah School of Medicine, Department of Pathology, and ARUP Laboratories