Fluorescence in situ Hybridization
Detects genetic abnormalities predictive of outcome in individuals with MM
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.
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:
- CKS1B (1q gain/amplification)
- FGFR3/IGH fusion t(4;14)
- ASS1 (+9)
- CCND1/IGH fusion t(11;14) and/or (+11)
- MAF/IGH fusion t(14;16)
- MAFB/IGH fusion t(14;20)
- TP53 (17p deletion)
Age of Onset
- Impaired renal function
- Bone disease (lesions)
FISH Testing and Prognostic Issues
Abnormalities are detected by conventional cytogenetics in ~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.
- 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
Swerdlow S, Campo E, Jaffe E, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th ed. International Agency for Research on Cancer, 2017.
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Multiple myeloma. Version 2.2020. [Accessed: Mar 2020]
Fonseca R, Bergsagel PL, Drach J, et al. International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia. 2009;23(12):2210-2221.
Rajan AM, Rajkumar SV. Interpretation of cytogenetic results in multiple myeloma for clinical practice. Blood Cancer J. 2015;5(10):e365.
Hanamura I, Stewart JP, Huang Y, et al. Frequent gain of chromosome band 1q21 in plasma-cell dyscrasias detected by fluorescence in situ hybridization: incidence increases from MGUS to relapsed myeloma and is related to prognosis and disease progression following tandem stem-cell transplantation. Blood. 2006;108(5):1724-1732.