Myeloid Malignancies and Acute Myeloid Leukemia Mutation Panels by Next Generation Sequencing

Myeloid malignancies are clonal disorders of hematopoietic stem and progenitor cells that include myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), myelodysplastic/myeloproliferative neoplasms (MDS/MPN), and acute myeloid leukemia (AML). Recent studies have identified recurrently mutated genes with diagnostic and/or prognostic impact in myeloid malignancies. The presence of certain mutations may inform clinical management. This multigene panel by massively parallel sequencing (next generation sequencing) is a more cost-effective approach when compared to the cost of multiple single gene tests. This test can be used to complement the morphologic and cytogenetic workup of myeloid malignancies.

Diagnostic Issues

• Genetic targets contained in panels are relevant across the spectrum of myeloid malignancies
• Identification of one or more clonal genetic abnormalities may aid in establishing the diagnosis and subclassification of a myeloid neoplasm
• Identification of certain variants or patterns of variants may aid in prognostication and clinical management of patients with a diagnosis of myeloid malignancy

Prognostic and Treatment Issues

• Certain variants or patterns of variants may have diagnostic or prognostic significance
• Certain variants may inform clinical management

Genes Tested: Myeloid Malignancies Mutation Panel by Next Generation Sequencing

ANKRD26, ASXL1, ASXL2, BCOR, BCORL1, BRAF, CALR, CBL, CBLB, CEBPA, CSF3R, CUX1, DDX41, DNMT1, DNMT3A, ELANE, ETNK1, ETV6, EZH2, FBXW7, FLT3, GATA1, GATA2, GNAS, HNRNPK, IDH1, IDH2, IL7R, JAK1, JAK2, JAK3, KDM6A, KIT, KMT2A, KRAS, LUC7L2, MPL, NOTCH1, NPM1, NRAS, NSD1, PHF6, PIGA, PPM1D, PRPF40B, PRPF8, PTPN11, RAD21, RUNX1, SAMD9, SAMD9L, SETBP1, SF3B1, SH2B3, SMC1A, SMC3, SRSF2, STAG2, STAT3, STAT5B, SUZ12, TET2, TP53, U2AF1, U2AF2, UBA1, WT1, ZRSR2

For some genes, one or more exons of the preferred transcript are not covered by sequencing for the indicated gene. See the Genes Tested table below for full list of targeted regions and exclusions.

Genes Tested: Acute Myeloid Leukemia Mutation Panel by Next Generation Sequencing

ANKRD26, ASXL1, CEBPA, DDX41, DNMT3A, ETV6, FLT3, GATA2, IDH1, IDH2, KIT, KRAS, NPM1, NRAS, RUNX1, TP53, WT1

For some genes, one or more exons of the preferred transcript are not covered by sequencing for the indicated gene. See the Genes Tested table below for full list of targeted regions and exclusions.

Test Interpretation

Results

• Positive: a somatic variant in one of the tested genes was detected
  • Clinical relevance will be described, if known
• Negative: no variants were detected in the sequenced genes

Limitations

• Not intended to detect minimal residual disease (MRD)
• Variants may be present below the limit of detection (LOD) of 5% allele frequency
• Variants greater than 24 base pairs may be detected at LOD, but the analytical sensitivity may be reduced
• Variants may not be identified due to technical limitations in the presence of pseudogenes or in repetitive or homologous regions
• Variants in regions that are not included in the preferred transcript for the targeted genes will not be detected; see Genes Tested table below for full list of targeted regions and exclusions

Analytic Sensitivity