title: Principles of analytical validation of next-generation sequencing based mutational analysis for hematologic neoplasms in a CLIA-certified laboratory.
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.
authors.affiliation: a Department of Hematopathology , The University of Texas at M.D. Anderson Cancer Center , Houston , TX , USA.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Kanagal-Shamanna
authors.affiliation: a Department of Hematopathology , The University of Texas at M.D. Anderson Cancer Center , Houston , TX , USA.
authors.forename: Rajesh R
authors.initials: RR
authors.lastname: Singh
authors.affiliation: a Department of Hematopathology , The University of Texas at M.D. Anderson Cancer Center , Houston , TX , USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Routbort
authors.affiliation: a Department of Hematopathology , The University of Texas at M.D. Anderson Cancer Center , Houston , TX , USA.
authors.forename: Keyur P
authors.initials: KP
authors.lastname: Patel
authors.affiliation: a Department of Hematopathology , The University of Texas at M.D. Anderson Cancer Center , Houston , TX , USA.
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.affiliation: a Department of Hematopathology , The University of Texas at M.D. Anderson Cancer Center , Houston , TX , USA.
authors.forename: Rajyalakshmi
authors.initials: R
authors.lastname: Luthra
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D019337:Hematologic Neoplasms / Q000175:diagnosis* / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing / Q000592:standards*; D006801:Humans; D025202:Molecular Diagnostic Techniques / Q000592:standards*; D009154:Mutation; D017422:Sequence Analysis, DNA / Q000592:standards*; D054928:Validation Studies as Topic
chemical_list: D014408:Biomarkers, Tumor
keywords: clinical laboratory; hematologic malignancies; mutation; next-generation sequencing; validation