FISH diagnostics in plasma cell myeloma: recommendations and own experience
Abstract
Plasma cell myeloma (PCM) is disease with heterogeneous clinical outcomes. It is increasingly evident that the genetic features of the tumor cells largely dictate the clinical heterogeneity of PCM. Primary chromosomal alterations in myeloma can be divided into hyperdiploid and non-hyperdiploid subtypes. Secondary chromosomal changes occur during progression of disease. Cytogenetic abnormalities are important prognostic markers in PCM and some of them were incorporated into the current prognostic staging system of PCM. The presence of t(4;14), t(14;16), t(14;20), gain of 1q or TP53 deletion is considered to be high-risk myeloma. Detection of these alterations can be performed by interphase fluorescence in situ hybridization (FISH) after separation or identification of the plasma cells. The proper FISH examination in myeloma has to meet further requirements regarding aspirating and timing of samples, probe selection and their cut-off levels, the criteria of accurate analysis and reporting. Based on the literature, we here present technical recommendations regarding FISH in PCM. Furthermore, we share our own experience in FISH diagnostics acquired over 12 years. In this period, we have performed nearly 2,050 FISH tests in 603 myeloma patients and used two different methods of myeloma FISH: FISH on immunolabeled plasma cells, and target FISH with the BioView system.
Keywords: myelomaplasmacytomaFISHcIGtarget FISHBioView
References
- Rajkumar SV. Multiple myeloma: 2020 update on diagnosis, risk-stratification and management. Am J Hematol. 2020; 95(5): 548–567.
- Schürch CM, Rasche L, Frauenfeld L, et al. A review on tumor heterogeneity and evolution in multiple myeloma: pathological, radiological, molecular genetics, and clinical integration. Virchows Arch. 2020; 476(3): 337–351.
- Fonseca R, Barlogie B, Bataille R, et al. Genetics and cytogenetics of multiple myeloma: a workshop report. Cancer Res. 2004; 64(4): 1546–1558.
- Barwick BG, Gupta VA, Vertino PM, et al. Cell of origin and genetic alterations in the pathogenesis of multiple myeloma. Front Immunol. 2019; 10: 1121.
- Ma ESK, Wang CLN, Wong ATC, et al. Target fluorescence in-situ hybridization (target FISH) for plasma cell enrichment in myeloma. Mol Cytogenet. 2016; 9: 63.
- Fonseca R, Bergsagel PL, Drach J, et al. International Myeloma Working Group. International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia. 2009; 23(12): 2210–2221.
- Caers Jo, Garderet L, Kortüm KM, et al. European Myeloma Network recommendations on tools for the diagnosis and monitoring of multiple myeloma: what to use and when. Haematologica. 2018; 103(11): 1772–1784.
- He H, Fu W, Jiang H, et al. The clinical characteristics and prognosis of IGH deletion in multiple myeloma. Leuk Res. 2015; 39(5): 515–519.
- Duek A, Trakhtenbrot L, Amariglio N, et al. Newly diagnosed multiple myeloma patients carrying monoallelic deletion of the whole locus of immunoglobulin heavy chain gene have a better prognosis compared to those with t(4;14) and t(14;16). Genes Chromosomes Cancer. 2019; 58(8): 516–520.
- Kumar SK, Mikhael JR, Buadi FK, et al. Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines. Mayo Clin Proc. 2009; 84(12): 1095–1110.
- Shah V, Sherborne AL, Walker BA, et al. Prediction of outcome in newly diagnosed myeloma: a meta-analysis of the molecular profiles of 1905 trial patients. Leukemia. 2018; 32(1): 102–110.
- Palumbo A, Avet-Loiseau H, Oliva S, et al. Revised International Staging System for Multiple Myeloma: a report from International Myeloma Working Group. J Clin Oncol. 2015; 33(26): 2863–2869.
- Ross FM, Avet-Loiseau H, Ameye G, et al. European Myeloma Network. Report from the European Myeloma Network on interphase FISH in multiple myeloma and related disorders. Haematologica. 2012; 97(8): 1272–1277.
- Hastings RJ, Cavani S, Bricarelli F, et al. Cytogenetic quidelines and quality assurance: a common European framework for quality assessment for constitutional and acquired cytogenetic investigations. Eur J Hum Genet. 2007; 15(5): 525–527.
- Rabani H, Ziv M, Lavi N, et al. Deletions and amplifications of the IGH variable and constant regions:a novel prognostic parameter in patients with multiple myeloma. Leuk Res. 2020; 99: 106476.
- Smith SC, Althof PA, Dave BJ, et al. High-risk cytogenetics in multiple myeloma: further scrutiny of deletions within the IGH gene region enhances risk stratification. Genes Chromosomes Cancer. 2020; 59(10): 569–574.