Test Catalog

Test ID: NGSMM    
NGSMM Next-Generation Sequencing (NGS), Multiple Myeloma

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

Evaluation of multiple myeloma at the time of diagnosis, for prognostic and potential therapeutic indications

 

Identification of 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 61 genes and intronic regions: AKT1, AKT2, AKT3, AKT3-G, ATM, B2M, BIRC2, BIRC3, BRAF, CCND1, CD38, CDK4, CDK7, CDKN1B, CDKN2A, CDKN2A-G, CRBN, CUL4A, CUL4B, CXCR4, DIS3, DIS3-G, EGFR, FAM46C, FGFR3, FGFR3-G, GRB2, IDH1, IDH2, IDH3A, IFNGR2, IGF1R, IKZF1, IKZF3, IL6, IL6R, IRF4, JAK2, KDM6A, KDM6A-G, KRAS, MYC, MYD88, NFKB2, NR3C1, NRAS, NSD2, PIK3CA, PIK3CG, PIK3R1, PIK3R1-G, PIK3R2, PIM1, PIM2, PIM3, PSMA1, PSMB5, PSMB5-G, PSMD1, PSMG2, PTPN11, RB1, STAT3, TGFBR2, TLR4, TP53, TRAF3, and XBP1.

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

See Targeted Genes Interrogated by Multiple Myeloma Next-Generation Sequencing in Special Instructions for a list of the genes and exons targeted by this assay.

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

Multiple myeloma (MM) is a malignancy of bone marrow plasma cells with an annual incidence of 200,000 per annum. Comprehensive clinical, radiologic and laboratory evaluation can initially stratify patients by disease phase and burden. Cytogenetic and FISH studies are important to help classify MM into standard, intermediate, and high risk groups. Advances in nontargeted therapies (including autologous bone marrow transplantation) have significantly improved the outcome of many patients; however, most patients with myeloma suffer relapse after initial treatment. Clinical next-generation sequencing (NGS) technology has enabled a deeper and more detailed evaluation of MM genetics. Testing allows for further risk categorization of the disease through the identification of additional abnormalities of prognostic and potentially therapeutic value. Application of targeted NGS-based analysis is a useful adjunct to the standard evaluation of MM patients at diagnosis and relapse. This test comprises a DNA-based multigene panel (NGSMM) that includes preanalytic plasma cell enrichment, NGS (Illumina platform), and detailed analysis resulted in a clinical report.

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

An interpretive report will be provided that includes the mutations (gene alterations) identified, if present.

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 61 genes and gene regions with variable full exon, partial region, or hot spot coverage (depending on specific locus). This test will, therefore, 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. 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 germ line alterations in analyzed gene regions, particularly with variant allele frequencies (VAF) near 50% or 100%. If nucleotide alterations in genes associated with germ line 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 calls detected between 5% and 10% VAF may indicate low-level (ie, subclonal) tumor populations, although the clinical significance of these findings may not be evident. 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.

 

NGS analysis should not be attempted if the plasma cell percentage is below approximately 15% by cytologic differential count, as the risk of insufficient target cell population enrichment is more likely, leading to assay failure.

 

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. Walker BA, Boyle, EM, Wardell CP, et al: Mutational spectrum, copy number changes, and outcome: results of a sequencing study of patients with newly diagnosed myeloma. J Clin Oncol 2015;33:3911-3920

2. Morgan GJ, Walker BA, Davies FE: The genetic architecture of multiple myeloma. Nat RevCancer. 2012;12(5):335-348

3. Kortuem KM, Braggio E, Bruins L, et al: Panel sequencing for clinically oriented variant screening and copy number detection in 142 untreated multiple myeloma patients. Blood Cancer J. 2016;6:e397

4. Kortuem KM, Mai EK, Hanafiah NH, et al: Targeted sequencing of refractory myeloma reveals a high incidence of mutations in CRBN and Ras pathway genes. Blood 2016;128:1226-1233

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