Multiple Myeloma Panel by FISH

Last Literature Review: May 2020 Last Update:

Aids in risk stratification of individuals with multiple myeloma. Recommended at initial diagnosis and in standard or low-risk individuals at time of disease progression.

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. Fluorescence in situ hybridization (FISH) testing for relevant markers should be performed upon diagnosis and in low-risk individuals at time of relapse to aid in risk stratification. 

Test Description

Plasma cells are isolated from a bone marrow (BM) aspirate using CD138+ microbeads. CD138+ cells (plasma cells) are then analyzed by FISH using specific probes for the following:

  • 1q (CKS1B) gain/amplification
  • t(4;14) (IGH/FGFR3 and MMSET fusion)
  • +9/9p (JAK2) enumeration
  • t(11;14) (IGH/CCND1 fusion and/or (+11))
  • t(14;16) (IGH/MAF fusion)
  • t(14;20) (IGH/MAFB fusion)
  • 17p (TP53) loss/deletion

Disease Overview


1.8% of all cancers in the U.S. 

Age of Onset

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


Presenting clinical features include symptoms of , :

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

FISH Testing and Prognostic Issues

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. Because most genetic subtypes in MM are primary, ploidy state, IGH translocation, and genetic status need only be assessed once at diagnosis.  However, repeat testing is justified in cases of gain/amplification of CKS1B (1q21) and deletion of TP53 (17p13), as these markers occur in disease progression and confer a worse ​prognosis. , 

Genetic Markers and Resulting Prognostic Issues
MarkersCharacteristics and Prognostic ValueRecurrent Testing 
Primary Cytogenetic Abnormalities


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

Presence: 40-60% of MM , 

Standard risk 

Infrequently occurs with IGH translocations , 

Panel tests two of the most commonly gained chromosomes (9, 11)

Test only once
t(4;14)(p16;q32) IGH-FGFR3/MMSET

Presence: 5% of MM , 

High to intermediate risk , 

Detectable only by FISH (cytogenetically cryptic)

Test only once
t(11;14)(q13;q32) IGH-CCND1

Presence: 15% of MM 

Standard risk , 

Test only once
t(14;16)(q32;q23) IGH-MAF

Presence: 5% of MM 

High risk , 

Test only once
t(14;20)(q32;q12) IGH-MAFB

Presence: 1-2% of MM , 

High risk , 

Test only once
Secondary Cytogenetic Abnormalities
Gain/amplification of 1q21 (CKS1B)

Presence: 30-70% of MM , 

Presence higher in disease progression

High risk

May be observed in hypodiploid, hyperdiploid, and IGH translocation-positive MM

Confers a poor prognosis in all subtypes

Repeat testing justified
Deletion 17p (TP53)

Presence: 5-10% of MM

Presence higher in disease progression

High risk , 

May be observed in hypodiploid, hyperdiploid, and IGH translocation-positive MM

Confers a poor prognosis in all subtypes

Repeat testing justified

Test Interpretation

Analytic Sensitivity/Specificity



  • Abnormal: gain/loss/rearrangement/translocation detected; percentage of cells affected (out of 100 or 200) reported
  • Normal: no evidence of gains, deletions, rearrangements, or translocations of loci tested


Only detects aberrations specific to probes used