Cytogenetic and FISH Analysis of 93 Multiple Myeloma Moroccan Patients

Overview

Journal Mol Genet Genomic Med

Specialty Genetics

Date 2020 Jun 24

PMID 32573970

Citations 10

Authors

Hasna Hamdaoui

Oumaima Benlarroubia

Oum Kaltoum Ait Boujmia

Hossein Mossafa

Karim Ouldim

Aziza Belkhayat

Imane Smyej

Houda Benrahma

Hind Dehbi

Fatima Chegdani

Affiliations

Soon will be listed here.

Abstract

Background: Multiple myeloma (MM) is a disease characterized by heterogeneous clinical presentations as well as complex genetic and molecular abnormalities. In MM, cytogenetic analysis is a challenge because of the low proliferation of malignant plasma cells. Thus, interphase fluorescence in situ hybridization (FISH), performed on sorted plasma cells detected abnormalities independently of a proliferative and infiltrative index. The purpose of this study was to explore, for the first time, the cytogenetic and molecular genetics features in Moroccan patients with multiple myeloma referred exclusively to National Reference Laboratory and to determine their risk stratification based on these features.

Methods: We performed cytogenetic analysis on 93 MM cases, all patients were subjected to FISH analysis, among which 45 patients have benefited from both FISH analysis and standard karyotype.

Results: Karyotype was normal in 78% (35/45) while, it was complex with varied structural and numerical abnormalities in 22% (10/45) of all patients, among which Hyperdiploid karyotype was found in 9% (n = 4 cases) and nonhyperdiploid in 13% (n = 6 cases). The most common numerical abnormalities were gains of chromosomes 3, 5, 9, 15, and 19. Whole chromosome losses were also frequent, affecting chromosomes X, 3, 14, 16 and 22. FISH analysis detected abnormalities in 50% of cases. The translocation t(4;14) and dup (1q) were the most frequent types of anomalies (14% and 13% respectively), followed by (17p) deletion and 14q32/IGH translocations with an undetermined origin (12% each) then the (1p) deletion (4%). For the normal karyotypes, FISH revealed chromosome abnormalities in 46%.

Conclusion: This study compares the results of cytogenetic analysis of chromosomal abnormalities in the Moroccan population with other countries. ½ patient showed at least one type of molecular genetic abnormalities. Therefore, the introducing of the cytogenetic analysis is obligatory in the diagnosis of multiple myeloma.

Citing Articles

Cytogenetic Alterations and Correlation with Age and Gender in Patients of Multiple Myeloma: A Study from a Tertiary Care Center in Eastern India.

Jha K, Saha S, Bhattacharyya M South Asian J Cancer. 2024; 13(2):126-131.

PMID: 38919660 PMC: 11196154. DOI: 10.1055/s-0043-1761441.

Cytogenetic, Clinical, Hematologic, Demographic, Immunohistochemical, and Flow Cytometry Characteristics of Patients with Plasma Cell Neoplasm in Five Years: A First Report from Iran.

Shokripour M, Hosseini S, Omidifar N, Mokhtari M, Safaei A Iran J Med Sci. 2024; 49(2):77-87.

PMID: 38356489 PMC: 10862103. DOI: 10.30476/IJMS.2023.96892.2855.

Quantitative assessment of bone marrow infiltration and characterization of tumor burden using dual-layer spectral CT in patients with multiple myeloma.

Xiong X, Hong R, Fan X, Hao Z, Zhang X, Zhang Y Radiol Oncol. 2024; 58(1):43-50.

PMID: 38183278 PMC: 10878765. DOI: 10.2478/raon-2024-0003.

Cytogenetic abnormalities correlate with clinico-biological characteristics in 30 Moroccan multiple myeloma patients.

Hamdaoui H, Nouadi B, Benlarroubia O, Chbel F, Saadoune C, Bennis F Leuk Res Rep. 2023; 20:100392.

PMID: 38035181 PMC: 10685041. DOI: 10.1016/j.lrr.2023.100392.

Clonal heterogeneity by fluorescence in situ hybridization in multiple myeloma: enhanced cytogenetic risk stratification.

Abdel-Qader H, Fouad D, Abuelela S, Ismail H, Boshnaq N Egypt J Med Hum Genet. 2023; 23(1):66.

PMID: 37521829 PMC: 8923967. DOI: 10.1186/s43042-022-00220-0.

References

Smadja N, Leroux D, Soulier J, Dumont S, Arnould C, Taviaux S . Further cytogenetic characterization of multiple myeloma confirms that 14q32 translocations are a very rare event in hyperdiploid cases. Genes Chromosomes Cancer. 2003; 38(3):234-9. DOI: 10.1002/gcc.10275. View

Kyle R, Gertz M, Witzig T, Lust J, Lacy M, Dispenzieri A . Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc. 2003; 78(1):21-33. DOI: 10.4065/78.1.21. View

Rajan A, Rajkumar S . Interpretation of cytogenetic results in multiple myeloma for clinical practice. Blood Cancer J. 2015; 5:e365. PMC: 4635200. DOI: 10.1038/bcj.2015.92. View

Avet-Loiseau H, Durie B, Cavo M, Attal M, Gutierrez N, Haessler J . Combining fluorescent in situ hybridization data with ISS staging improves risk assessment in myeloma: an International Myeloma Working Group collaborative project. Leukemia. 2012; 27(3):711-7. PMC: 3972006. DOI: 10.1038/leu.2012.282. View

Moreau P, San Miguel J, Sonneveld P, Mateos M, Zamagni E, Avet-Loiseau H . Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017; 28(suppl_4):iv52-iv61. DOI: 10.1093/annonc/mdx096. View

Avet-Loiseau H, Hulin C, Campion L, Rodon P, Marit G, Attal M . Chromosomal abnormalities are major prognostic factors in elderly patients with multiple myeloma: the intergroupe francophone du myélome experience. J Clin Oncol. 2013; 31(22):2806-9. PMC: 3718879. DOI: 10.1200/JCO.2012.46.2598. View

Nishida K, Tamura A, Nakazawa N, Ueda Y, Abe T, Matsuda F . The Ig heavy chain gene is frequently involved in chromosomal translocations in multiple myeloma and plasma cell leukemia as detected by in situ hybridization. Blood. 1997; 90(2):526-34. View

Wang C, Wu J, Yang K, Su M, Zhang H, Pan Y . [Retrospective Analysis of Genetics Abnormalities in Patients with Multiple Myeloma]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2018; 26(6):1681-1687. DOI: 10.7534/j.issn.1009-2137.2018.06.017. View

Palumbo A, Anderson K . Multiple myeloma. N Engl J Med. 2011; 364(11):1046-60. DOI: 10.1056/NEJMra1011442. View

10.

Lloveras E, Granada I, Zamora L, Espinet B, Florensa L, Besses C . Cytogenetic and fluorescence in situ hybridization studies in 60 patients with multiple myeloma and plasma cell leukemia. Cancer Genet Cytogenet. 2003; 148(1):71-6. DOI: 10.1016/s0165-4608(03)00233-4. View

11.

Kumar S, Fonseca R, Ketterling R, Dispenzieri A, Lacy M, Gertz M . Trisomies in multiple myeloma: impact on survival in patients with high-risk cytogenetics. Blood. 2012; 119(9):2100-5. PMC: 3311247. DOI: 10.1182/blood-2011-11-390658. View

12.

Kishimoto R, de Freitas S, Ratis C, Borri D, Sitnik R, Velloso E . Validation of interphase fluorescence in situ hybridization (iFISH) for multiple myeloma using CD138 positive cells. Rev Bras Hematol Hemoter. 2016; 38(2):113-20. PMC: 4877610. DOI: 10.1016/j.bjhh.2016.01.005. View

13.

Mikhael J, Dingli D, Roy V, Reeder C, Buadi F, Hayman S . Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines 2013. Mayo Clin Proc. 2013; 88(4):360-76. DOI: 10.1016/j.mayocp.2013.01.019. View

14.

Hamdaoui H, Benlarroubia O, Ait Boujmia O, Mossafa H, Ouldim K, Belkhayat A . Cytogenetic and FISH analysis of 93 multiple myeloma Moroccan patients. Mol Genet Genomic Med. 2020; 8(9):e1363. PMC: 7507047. DOI: 10.1002/mgg3.1363. View

15.

Rajkumar S, Gupta V, Fonseca R, Dispenzieri A, Gonsalves W, Larson D . Impact of primary molecular cytogenetic abnormalities and risk of progression in smoldering multiple myeloma. Leukemia. 2013; 27(8):1738-44. PMC: 3773463. DOI: 10.1038/leu.2013.86. View

16.

Mohamed A, Bentley G, Bonnett M, Zonder J, Al-Katib A . Chromosome aberrations in a series of 120 multiple myeloma cases with abnormal karyotypes. Am J Hematol. 2007; 82(12):1080-7. DOI: 10.1002/ajh.20998. View

17.

Avet-Loiseau H, Facon T, Grosbois B, Magrangeas F, Harousseau J, Minvielle S . Oncogenesis of multiple myeloma: 14q32 and 13q chromosomal abnormalities are not randomly distributed, but correlate with natural history, immunological features, and clinical presentation. Blood. 2002; 99(6):2185-91. DOI: 10.1182/blood.v99.6.2185. View

18.

Neben K, Jauch A, Hielscher T, Hillengass J, Lehners N, Seckinger A . Progression in smoldering myeloma is independently determined by the chromosomal abnormalities del(17p), t(4;14), gain 1q, hyperdiploidy, and tumor load. J Clin Oncol. 2013; 31(34):4325-32. DOI: 10.1200/JCO.2012.48.4923. View

19.

Hartmann L, Biggerstaff J, Chapman D, Scott J, Johnson K, Ghirardelli K . Detection of genomic abnormalities in multiple myeloma: the application of FISH analysis in combination with various plasma cell enrichment techniques. Am J Clin Pathol. 2011; 136(5):712-20. DOI: 10.1309/AJCPF7NFLW8UAJEP. View

20.

Rajkumar S, Dimopoulos M, Palumbo A, Blade J, Merlini G, Mateos M . International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014; 15(12):e538-48. DOI: 10.1016/S1470-2045(14)70442-5. View