Multiple Myeloma Cytogenetic Analysis

Your key to improving the diagnostic process with quality cytogenetic analysis

Multiple myeloma, a heterogeneous disease with a high mortality rate1,2

While less common than other blood-related cancers, the burden of multiple myeloma continues to grow.3,4 Since 1990, the global incidence of cases has increased over 125%, and in 2022, the American Cancer Society estimated 34,470 new cases and around 12,640 deaths in the United States alone.3,5

Despite these figures, new treatments and advances in diagnostic technologies continue to improve outcomes in MM.6The Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute (NCI) reports that in 1975, the 5-year relative survival rate for myeloma was 25% and steadily increased to 58% in 2019.7 Perhaps more importantly, for the 4% of people who are diagnosed at an early stage, this rate has increased to 77%.4 Early diagnosis has, therefore, become one of the goals in the challenge to redefine what’s possible for people living with MM.

Cytogenetic abnormalities associated with MM are detectable long before symptomatic disease8,9

Multiple myeloma is characterized by the accumulation of malignant plasma cells in the bone marrow.10 Affected cells produce monoclonal immunoglobulin and invade and destroy adjacent bone tissue.11 The collection of cytogenetic abnormalities present at diagnosis is the driving force behind not only the clinical presentation of MM, but also response to treatment and overall prognosis.1,12

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Testing Methods
The pathway to active MM

MM almost always starts with premalignant monoclonal gammopathy of undetermined significance (MGUS).1,13

Testing Methods
Smoldering multiple myeloma (SMM)

MGUS may progress to SMM at a rate of 1% per year.1,6,14

Testing Methods
Active multiple myeloma (MM)

SMM may progess to active MM.1,13,14 The risk of SMM progressing to active MM averages 25% per year for the first 2 years, declining to 1% after 10 years following diagnosis.6

male staring out of window

Cytogenetic analysis is recommended for all suspected MM cases15

Performing a plasma cell fluorescence in situ hybridization (FISH) panel on bone marrow is an essential part of the initial diagnostic workup for MM, and for R-ISS staging of the disease.15,16

Translocations—occurrences of one piece of a chromosome breaking off and attaching to a different chromosome—are common in MM, with IgH translocations occurring in 50-70% of cases.17,18

Translocations of IgH locus18

Translocation Gene(s) Prevalence
t(11;14)(q13;q32) CCND1 15% to 20%
t(4;14)(p16;q32) FGFR3 and MMSET 10% to 15%
t(14;16)(q32;q23) MAF 2% to 5%
t(6;14)(p21;q32) CCND3 2%
t(14;20)(q32;q12) MAFB 1%

CCND1 = cyclin D1; FGFR3 = fibroblast growth factor receptor 3; MMSET = multiple myeloma SET domain; MAF = v-maf musculoaponeurotic fibrosarcoma oncogene homolog; CCND3 = cyclin D3; MAFB = v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog B.


mSMART 3.0 classification of risk events in active MM*19

High-risk Standard-risk*
  • t(4;14)
  • t(14;16)
  • t(14;20)
  • del(17p)
  • Non-hyperdiploid
  • t(11;14)
  • t(6;14)
  • Hyperdiploid

*This is not an exhaustive list.

Standard risk is defined as having an indolent course of disease and lengthy survival, while high-risk patients experience a more aggressive course and shorter survival.20,21

The importance of comprehensive cytogenetic analysis

Classifying MM early on during diagnosis is important for distinguishing it from other plasma cell neoplasm.22 To treat patients effectively, it is recommended that all patients undergo cytogenetic evaluation at diagnosis. Although the most information is gained when both conventional cytogenetic and fluorescence in situ hybridization (FISH) testing are performed, not all centers have access to both.20 With the additional information gained by FISH, it is the preferred modality if both are not available.20

IMWG recommends FISH testing with plasma cell enrichment (PCE) to reduce risk of low sensitivity for detection of chromosome abnormalities.29

Enhance the sensitivity of your FISH results with PCE

Because key decisions rely on accurate information, it is important that testing be performed appropriately. FISH is the standard of care for cytogenetic analysis in MM;23 however, compared to other hematological neoplasms, accurate FISH testing is more complicated and more time-consuming in MM.13

Accuracy of results is challenged by the dilution effect of bone marrow specimens and poor growth of plasma cells ex vivo; in some cases, total plasma cell percentage can be less than 10%.24 PCE is a process of cell separation that isolates the cells of cancerous origin.25 This enriched sample can then be analyzed with higher specificity.26 Performing FISH without undergoing PCE limits the efficacy of the assay, leading to both reduced sensitivity for translocations and an increased risk of false negatives.24

Institutional challenges also exist with cytogenetic testing as there are no uniform practices, and significant variability exists both within and between laboratories with respect to methodology, including number of cells analyzed per sample, cell selection methodology, and number of probes used.23

PCE can increase cell percentages to as much as 96% and improve detection of cytogenetic abnormalities 3-fold when used with FISH.27

Multiple PCE modalities exist for FISH:

  • Magnetic-activated cell sorting (MACS)24
  • Fluorescence-activated cell sorting (FACS)24
  • Flow cytometry18
  • Plasma cell staining10

According to College of American Pathologists (CAP), PCE can improve the sensitivity of the FISH panel, decreasing the risk for false-negative results.10,28

FISH at NeoGenomics

NeoGenomics has been offering high-quality FISH testing with PCE for over 10 years, having pioneered technical-only FISH testing and completing over 100,000 tech-only cases since. 

We’ve provided our clients with high-quality FISH testing with PCE as part of a thorough menu of customizable panels and probes for fast, cost-effective diagnostics of myeloma disorders.


Ordering Options

FISH tests can be ordered as disease-specific panels. Probe sets within panels may be ordered individually for detection of single abnormalities, available in global and tech-only options.

  • Please ensure sample is received at NeoGenomics Laboratories within 72 hours of collection to perform PCE.
  • Turnaround time for FISH testing with PCE is 4–5 days.

To order cytogenetic testing, NeoGenomics offers the following tests:

See complete test details


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  2. Xiang Y, et al. Front Oncol. 2021;11:698197.
  3. Cancer Network. Accessed February 4, 2022.
  4. Cancer.Net. Accessed February 4, 2022.
  5. American Cancer Society. Accessed February 4, 2022.
  6. Bolli N, et al. Front Oncol. 2020;10(189):1-15.
  7. Syned MJ, et al. BMC Cancer. 2021;21:821.
  8. Capp J-P, Bataille R. Front Oncol. 2018;8:355.
  9. Fonseca R, et al. Blood. 2002;100(4):1417-1424.
  10. Hartmann L, et al. Am J Clin Pathol. 2011;136:712-720.
  11. Merck Manuals. Professional Edition. Accessed February 4, 2022.
  12. Smadbeck JB, et al. Blood. 2021;138:3771-3772.
  13. Woroniecka R. Acta Haematol Pol. 2021;52(4):390-396.
  14. Mateos M-V, et al. Blood Cancer J. 2020;10:102.
  15. Dimopoulos MA, et al. Ann Oncol. 2021;32(3):309.
  16. Moreau P, et al. Ann Oncol. 2017(Suppl4):iv52-iv61.
  17. National Cancer Institute. Dictionary of Cancer Terms. Accessed February 4, 2022.
  18. Saxe D, et al. Int J Lab Hematol. 2019;41(1):5-14.
  19. mSMART Risk stratification of newly diagnosed myeloma. Accessed February 4, 2022.
  20. Mikhael JR, et al. Mayo Clin Proc. 2013;88(4):360-376.
  21. Kumar SK, et al. Mayo Clin Proc. 2009;84(12):1095-1110.
  22. Kumar S, et al. Best Pract Res Clin Haematol. 2010;23(3):433-451.
  23. Yu Y, et al. JCO Oncol Pract. 2020;16(10):e1169.
  24. Miller C, et al. Blood. 2016;128(22):374.
  25. Minges HA, et al. J Immunol Methods. 2008;329(1-2):219-224.
  26. Pozdnyakova O, et al. Cancer Genet Cytogenet. 2009;189(2):112-117.
  27. Lu G, et al. Arch Pathol Lab Med. 2013;137(5):625-631.
  28. College of American Pathologists. Accessed February 17, 2022.
  29. Fonseca R, et al. Leukemia. 2009 Dec;23(12):2210-21

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