This test is a targeted next-generation sequencing (NGS) assay that encompasses 11 genes with variable full exon, partial region (including select intronic or noncoding 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 near 50% or 100%. If nucleotide alterations in genes associated with germline variant syndromes are present and there is a strong clinical suspicion or family history of malignant disease predisposition, additional genetic testing and appropriate counseling may be indicated. 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), and these may not be clearly distinguishable from tumor-associated mutations. Some apparent mutations classified as variants of uncertain significance may represent rare or low-frequency polymorphisms.
Prior treatment for hematologic malignancy could affect the results obtained in this assay. In particular, a prior allogeneic hematopoietic stem cell transplant may cause difficulties in resolving somatic or polymorphic alterations or assigning variant calls correctly to donor and recipient fractions, if pertinent clinical or laboratory information (eg, chimerism engraftment status) is not provided.
The finding of a genetic alteration does not necessarily indicate the presence of a myeloid neoplasm. Correlation with clinical, histopathologic, and additional laboratory findings is required for final interpretation of NGS results and is the responsibility of the managing physician.