Design of targeted, capture-based, next generation sequencing tests for precision cancer therapy

Abstract

In cancer medicine, next generation sequencing (NGS) has emerged as a practical method to generate patient- and tumor-specific genetic data for optimal selection of targeted therapies. Targeted sequencing allows clinical testing to focus on cancer-related genes, thus maximizing the test's sensitivity and specificity for actionable variants. In this review, we summarize the current regulatory environment surrounding clinical NGS, including regulations and professional opinions established by the College of American Pathologists, the Centers for Disease Control and Prevention, the Clinical Laboratory Improvement Amendments, the Clinical and Laboratory Standards Institute, the Association for Molecular Pathology, the New York State Department of Health, and the American College of Medical Genetics. We outline practical considerations for the design of targeted NGS assays, with an emphasis on capture-based methods. Finally, we discuss components of the validation process for clinical NGS assays as well as challenges that still remain for clinical NGS.

Keywords: Massively parallel sequencing; laboratory standards; regulatory compliance; validation studies.