Principles of analytical validation of next-generation sequencing based mutational analysis for hematologic neoplasms in a CLIA-certified laboratory

Expert Rev Mol Diagn. 2016;16(4):461-72. doi: 10.1586/14737159.2016.1142374. Epub 2016 Feb 15.

Abstract

Targeted therapy based on mutational profiles is the current standard of practice for the management of patients with hematologic malignancies. Next-generation sequencing (NGS)- based analysis has been adopted by clinical laboratories for high-throughput mutational profiling of myeloid and lymphoid neoplasms. The technology is fairly novel and complex, hence both validation and test implementation in a CLIA-certified laboratory differ substantially from traditional sequencing platforms. Recently, organizations such as the American College of Medical Genetics, Centers for Disease Control and Prevention and College of American Pathologists have published principles and guidelines for NGS test development to ensure standardization of testing across institutions. Summarized here are the recommendations from these organizations as they pertain to targeted NGS-based testing of hematologic malignancies ('liquid tumors'), with particular emphasis on myeloid neoplasms.

Keywords: clinical laboratory; hematologic malignancies; mutation; next-generation sequencing; validation.

Publication types

  • Review

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Hematologic Neoplasms / diagnosis*
  • Hematologic Neoplasms / genetics
  • High-Throughput Nucleotide Sequencing / standards*
  • Humans
  • Molecular Diagnostic Techniques / standards*
  • Mutation
  • Sequence Analysis, DNA / standards*
  • Validation Studies as Topic*

Substances

  • Biomarkers, Tumor