Test Catalog

Test ID: NGSHM    
OncoHeme Next-Generation Sequencing for Myeloid Neoplasms, Varies

Useful For Suggests clinical disorders or settings where the test may be helpful

Evaluation of hematologic neoplasms, specifically of myeloid origin (eg, acute myeloid leukemia, myelodysplastic syndrome, myeloproliferative neoplasm, myelodysplastic/myeloproliferative neoplasm) at the time of diagnosis or possibly disease relapse, to help determine diagnostic classification and provide prognostic or therapeutic information for clinical management

 

Determine the presence of new clinically important gene mutation changes at relapse

Genetics Test Information Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test includes next-generation sequencing to evaluate for the following 42 genes and select intronic regions: ANKRD26, ASXL1, BCOR, CALR, CBL, CEBPA, CSF3R, DDX41, DNMT3A,ELANE, ETNK1, ETV6, EZH2, FLT3, GATA1, GATA2, IDH1, IDH2, JAK2, KDM6A, KIT, KRAS, MPL, NPM1, NRAS, PHF6, PTPN11, RAD21, RUNX1, SETBP1, SH2B3, SF3B1, SRP72, SMC3, SRSF2, STAG2,TERT, TET2, TP53, U2AF1, WT1, and ZRSR2.

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

The following are available in Special Instructions:

-Targeted Genes Interrogated by OncoHeme Next-Generation Sequencing; this is a list of the genes and exons targeted by this test.

-Myelodysplastic Syndrome: Guideline to Diagnosis and Follow-up

-Myeloproliferative Neoplasm: A Diagnostic Approach to Bone Marrow Evaluation

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Next-generation sequencing (NGS) is a comprehensive molecular diagnostic methodology that can interrogate multiple regions of genomic tumor DNA in a single assay. Many hematologic neoplasms are characterized by morphologic or phenotypic similarities, but can have characteristic somatic mutations in many genes. In addition, many myeloid neoplasms lack a clonal cytogenetic finding at diagnosis (normal karyotype) but can be diagnosed and classified according to the gene mutation profile. The presence and pattern of gene mutations can provide critical diagnostic, prognostic, and sometimes therapeutic information for the managing physicians.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation Provides information to assist in interpretation of the test results

Mutations (gene alterations) identified, if present, using human reference genome build GRCh37 (hg19). An interpretive report will be provided.

 

If this test is ordered in the setting of erythrocytosis and suspicion of polycythemia vera, interpretation requires correlation with a concurrent or recent prior bone marrow evaluation.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This test is a targeted next-generation sequencing (NGS) (panel) assay that encompasses 42 genes with variable full exon, partial region (including select intronic or non-coding regions), or hot spot coverage (depending on specific locus). Therefore, this test will not detect other genetic abnormalities in genes or regions outside the specified target areas. The test detects single base substitutions (ie, point mutations), as well as small insertion or deletion type events, but it does not detect gene rearrangements (ie, translocations), gene fusions, copy number alterations, or large scale (segmental chromosome region) deletions and complex changes.

 

This assay does not distinguish between somatic and germline alterations in analyzed gene regions, particularly with variant allele frequencies (VAF) near 50% or 100%. If nucleotide alterations in genes associated with germline mutation syndromes are present and there is also a strong clinical suspicion or family history of malignant disease predisposition, additional genetic testing and appropriate counseling may be indicated. Mutation cells detected between 5% and 10% VAF may indicate low-level (ie, subclonal) tumor populations, although the clinical significance of these findings may not be clear. A low incidence of gene mutations associated with myeloid neoplasms can be detected in nonmalignant hematopoietic cells in individuals with advancing age (clonal hematopoiesis of indeterminate potential, CHIP) and these may not be clearly distinguishable from tumor-associated mutations. Some apparent mutations classified as variants of undetermined significance (VUS) may represent rare or low frequency polymorphisms.

 

Prior treatment for hematologic malignancy could affect the results obtained in this assay. In particular, prior allogeneic hematopoietic stem cell transplant (HSCT) may cause difficulties in resolving somatic or polymorphic alterations, or in assigning variant calls correctly to donor and recipient fractions, if pertinent clinical or laboratory information (eg, chimerism engraftment status) is not provided.

 

Correlation with clinical, histopathologic and additional laboratory findings is required for final interpretation of these results. The final interpretation of results for clinical management of the patient is the responsibility of the managing physician.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Patel JP, Levine RL: How do novel molecular genetic markers influence treatment decisions in acute myeloid leukemia? Hematology Am Soc Hematol Educ Program 2012;2012:28-34

2. Lindsley RC, Ebert BL: The biology and clinical impact of genetic lesions in myeloid malignancies. Blood 2013;23:3741-3748

3. Patel JP, Gonen M, Figueroa ME, et al: Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med 2012;366:1079-1089

4. Haferlach T, Nagata Y, Grossman V, et al: Landscape of genetic lesions in 944 patients with myelodysplastic syndromes. Leukemia 2014;28:241-247

5. Vainchenker W, Delhommeau F, Constantinescu SN, Bernard OA: New mutations and pathogenesis of myeloproliferative neoplasms. Blood 2011;118:1723-1735

Special Instructions Library of PDFs including pertinent information and forms related to the test