Myeloid Malignancies Mutation Panel by Next Generation Sequencing

For more information on genomic microarray testing in oncology, see the additional technical information document, Cytogenomic Microarray – Oncology

See Related Tests

For additional test information, including information on individual tests, refer to the Acute Myeloid Leukemia Molecular Genetic Testing Test Fact Sheet

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.

Disease Overview

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

Genetics

Genes Tested

ANKRD26, ASXL1, ASXL2, BCOR, BCORL1, BRAF, CALR, CBL, CBLB, CEBPA, CSF3R, CUX1a, DDX41, DNMT1a, DNMT3A, ELANE, ETNK1, ETV6, EZH2, FBXW7, FLT3, GATA1, GATA2, GNAS, HNRNPK, IDH1, IDH2, IL7R, JAK1, JAK2, JAK3, KDM6Aa, KIT, KMT2A, KRAS, LUC7L2, MPL, NOTCH1, NPM1a, NRAS, NSD1, PHF6, PIGA, PRPF40B, PRPF8, PTPN11, RAD21, RUNX1, SETBP1, SF3B1, SH2B3, SMC1A, SMC3, SRSF2, STAG2, STAT3, STAT5Ba, SUZ12a, TET2, TP53, U2AF1, U2AF2, WT1, ZRSR2

 (aOne or more exons of the preferred transcript  are not covered by sequencing for the indicated gene. See 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

Analytical Sensitivity

Variant Class Analytical Sensitivity (PPA)a Estimate (%) Analytical Sensitivity (PPA) 95% Credibility Regiona (%)

SNVs

96.9%

95.1-98.1%

Insertions/Duplications (1-24bp)

98.1%

95.5-99.3%

Insertions/Duplications (>24bp)

> 99%

92.9-100.0%

Deletions (1-24bp)

96.7%

92.8-98.7%

Deletions (>24bp)

90%

79.5-96.1%

MNVs

97%

93.0-99.0%

FLT3 ITDs

> 99%

97.1-100.0%

aGenes included on this test are a subset of a larger methods-based validation from which the PPA values are derived.

bp, base pairs; ITDs, internal tandem duplications; MNVs, multinucleotide variants; PPA, positive percent agreement; SNVs, single nucleotide variants

Genes Tested
Gene Preferred Transcripta Excluded Exonsb

ANKRD26

NM_014915

 

ASXL1

NM_015338

 

ASXL2

NM_018263

 

BCOR

NM_001123385

 

BCORL1

NM_021946

 

BRAF

NM_004333

 

CALR

NM_004343

 

CBL

NM_005188

 

CBLB

NM_170662

 

CEBPA

NM_004364

 

CSF3R

NM_156039

 

CUX1

NM_181552

24

DDX41

NM_016222

 

DNMT1

NM_001130823

5

DNMT3A

NM_175629

 

ELANE

NM_001972

 

ETNK1

NM_018638

 

ETV6

NM_001987

 

EZH2

NM_004456

 

FBXW7

NM_033632

 

FLT3

NM_004119

 

GATA1

NM_002049

 

GATA2

NM_032638

 

GNAS

NM_000516

 

HNRNPK

NM_002140

 

IDH1

NM_005896

 

IDH2

NM_002168

 

IL7R

NM_002185

 

JAK1

NM_002227

 

JAK2

NM_004972

 

JAK3

NM_000215

 

KDM6A

NM_001291415

13

KIT

NM_000222

 

KMT2A

NM_001197104

 

KRAS

NM_004985

 

LUC7L2

NM_016019

 

MPL

NM_005373

 

NOTCH1

NM_017617

 

NPM1

NM_002520

1

NRAS

NM_002524

 

NSD1

NM_022455

 

PHF6

NM_001015877

 

PIGA

NM_002641

 

PRPF40B

NM_001031698

 

PRPF8

NM_006445

 

PTPN11

NM_002834

 

RAD21

NM_006265

 

RUNX1

NM_001754

 

SETBP1

NM_015559

 

SF3B1

NM_012433

 

SH2B3

NM_005475

 

SMC1A

NM_006306

 

SMC3

NM_005445

 

SRSF2

NM_003016

 

STAG2

NM_001042749

 

STAT3

NM_139276

 

STAT5B

NM_012448

6-9

SUZ12

NM_015355

1-9

TET2

NM_001127208

 

TP53

NM_000546

 

U2AF1

NM_006758

 

U2AF2

NM_007279

 

WT1 NM_024426  
ZRSR2 NM_005089  

aThis is the transcript number used for analyzing and reporting variants. The transcript version number may change periodically and thus is not listed here. The transcript with version number will be included on the patient's report if a variant is detected in the gene.

bNoncoding exons are not analyzed, except for regions containing known clinically relevant variants in the ANKRD26 5’UTR and NOTCH1 3’UTR. In addition, coding exons noted here are not sequenced due to technical limitations of the assay.