Multiple Myeloma Panel by FISH

Last Literature Review: April 2024 Last Update:

Aids in risk stratification of individuals with plasma cell neoplasms (monoclonal gammopathy of unknown significance [MGUS], smoldering multiple myeloma [SMM], multiple myeloma [MM]). Recommended at initial diagnosis and/or at disease progression. Refer to companion test for monitoring.

Companion test:

Use to monitor for a previously identified clone.

Multiple myeloma (MM) is a plasma cell dyscrasia that can evolve from a premalignant monoclonal gammopathy. Prognosis often depends on the presence or absence of particular genetic markers. Bone marrow aspirate and biopsy with fluorescence in situ hybridization (FISH) testing for relevant markers should be performed as clinically indicated, including upon diagnosis and in low-/standard-risk individuals at time of relapse to aid in risk stratification. , 

Test Description

This test involves the performance of FISH on CD138+ enriched cells (assuming the specimen is sufficient for enrichment) for multiple myeloma prognosis-specific genomic abnormalities:

  • 1p (CDKN2C loss/deletion)/1q (CKS1B gain/amplification)
  • 17p (TP53 loss/deletion)/17q (NF1) control
  • t(4;14) (IGH/FGFR3 or NSD2 [MMSET] fusion)
  • t(11;14) (IGH/CCND1 fusion and/or +11)
  • t(14;16) (IGH/MAF fusion)
  • t(14;20) (IGH/MAFB fusion)

Disease Overview

Age of Onset

Most frequently diagnosed between ages 65 and 74 years (median age 69 years) 

Symptoms

Presenting clinical features include symptoms of , :

  • Hypercalcemia
  • Impaired renal function
  • Anemia
  • Bone disease (lesions)

Clinical Implications of Tested Genomic Abnormalities

Abnormalities are detected by conventional cytogenetics in approximately 30% of MMs. FISH testing increases this number to >90%.  Cytogenetic abnormalities affect the prognosis of patients with MM.

Genetic Markers and Clinical Implications: Multiple Myeloma Panel by FISH
Included MarkersClinical ImplicationsRecurrent Testing

Primary Cytogenetic Abnormalities

t(4;14) (IGH/FGFR3 or NSD2 [MMSET] fusion)

Presence: 15% of MM

High risk

Detectable only by FISH (cytogenetically cryptic)

Test only once
t(11;14) (IGH/CCND1 fusion and/or +11)

Presence: 15-20% of MM

Standard risk

Test only once
t(14;16) (IGH/MAF fusion)

Presence: 3-5% of MM

High risk

May be missed by karyotyping

Test only once
t(14;20) (IGH/MAFB fusion)

Presence: 1-2% of MM

High risk

Test only once

Hyperdiploidy

 

Usually gains (trisomies) of three or more odd-numbered chromosomes (3, 5, 7, 9, 11, 15, 19, 21)

Presence: 50% of MM

Standard risk

Infrequently occurs with IGH translocations

Panel tests the commonly gained chromosome 11

Test only once

Secondary Cytogenetic Abnormalities

1q (CKS1B gain/amplification)

  • 1q21 gain defined as 3 copies
  • 1q21 amplification defined as ≥4 copies
     

Presence: 30-40% of MM

Presence higher in disease progression

High risk (in the presence of other abnormalities)

May co-occur with primary and other secondary cytogenetic abnormalities

Confers a poor prognosis in all subtypes

Repeat testing justified
1p (CDKN2C loss/deletion)

Presence: 8-12% of MM

Presence higher in disease progression

High risk

May co-occur with primary and other secondary cytogenetic abnormalities

Confers a poor prognosis in all subtypes

Repeat testing justified
17p (TP53 loss/deletion)

Presence: 7-10% of MM

Presence higher in disease progression

High risk

May co-occur with primary and other secondary cytogenetic abnormalities

Confers a poor prognosis in all subtypes

Repeat testing justified
Sources: NCCN 2024 ; Hagen 2022 ; Rajkumar, 2022 ; Rajan, 2015 

Test Interpretation

Analytic Sensitivity/Specificity

>95%

Results

Results Interpretation: Multiple Myeloma Panel by FISH
Result ReportedGenomic Abnormalities DetectedInterpretation and Clinical Implications
Normal FISH resultNone

No evidence of any of the tested abnormalities

Other abnormalities (for which this test does not include probes) are not excluded

Abnormal FISH result (specific abnormalities will be reported)One or more

Results suggest a clonal population of cells with clinical significance in MGUS, MM, and/or SMM

Results should be correlated with clinical and other laboratory findings

Use companion test 3002737 to monitor for positive results by FISH in future studies

Limitations

  • This test only detects genomic abnormalities specific to the probes used.
  • When this test is ordered in conjunction with chromosome analysis (karyotype) and/or genomic microarray on low cellularity samples, this test will be prioritized due to the need for CD138+ cell enrichment prior to FISH.
    • Microarray will be prioritized after FISH, followed by karyotype.
    • This may impact the completion of lower priority tests.
  • If enrichment fails yield to sufficient CD138+ cells, testing will be performed using unenriched cells if available.

References