THE IMPORTANCE OF TARGETED NEXT-GENERATION SEQUENCING USAGE IN CYTOGENETICALLY NORMAL MYELOID MALIGNANCIES Targeted next-generation sequencing usage in cytogenetically normal myeloid malignancies
Main Article Content
Keywords
Keywords: Hematologic malignancies, NGS, karyotype, FISH
Abstract
Advanced diagnostic methods give an advantage for the identification of the abnormalities in myeloid malignancies. Various researchers have shown the potential importance of genetic tests both before the onset of the disease and during the remission. Large testing panels prevents false negative results in myeloid malignancies. But the important question is how the results of conventional cytogenetic and molecular cytogenetic techniques can be merged together with NGS technologies. In this paper, we drew an algorithm for evaluation of the myeloid malignancies. In order to evaluate genetic abnormalities, we performed cytogenetics, molecular cytogenetics and NGS testing in hematologic malignancies. In this study, we analyzed 100 patients who admitted to Medical Genetics Laboratory within different type of myeloid malignancies. We highlighted the possible diagnostic algorithm for cytogenetically normal cases. We applied NGS 141 gene panel for cytogenetically normal patients and we detected two or more pathogenic variations in 61 out of 100 patients (61%). The pathogenic variation detection rate of NGS varies in disease groups: AML were 85% and MDS were 23%. Here, we identified 24 novel variation out of total pathogenic variations in myeloid malignancies. A total 18 novel variation were identified in AML and 6 novel variation were identified in MDS. Despite of long turnaround time, conventional techniques are still golden standard for myeloid malignancies but sometimes cryptic gene fusions or complex abnormalities cannot be identified easily by conventional techniques. In these conditions, advanced technologies like NGS are highly recommended.
Downloads
Abstract 1034
PDF Downloads 372
HTML Downloads 127
References
2. Palumbo, G.A. et al.; The Role of New Technologies in Myeloproliferative Neoplasms. Front Oncol. 2019 Apr 26;9:321. doi: 10.3389/fonc.2019.00321. eCollection 2019.
3. Bacher, U.; et al. Challenges in the introduction of next-generation sequencing (NGS) for diagnostics of myeloid malignancies into clinical routine use. Blood Cancer J. 2018 Nov 12;8(11):113. Doi: 10.1038/s41408-018-0148-6.
4. Shumilov, E. et al.; Current status and trends in the diagnostics of AML and MDS. Review article. Blood Rev. 2018. https://doi.org/10.1016/j.blre.04.008.
5. Barbui, T. et al.; The 2016 WHO classification and diagnostic criteria for myeloproliferative neoplasms: document summary and in-depth discussion. Blood Cancer J. 8, 2018. https://doi.org/10.1038/s41408-018-0054-y
6. Cazzola, M., Della Porta, M. G. & Malcovati, L.; The genetic basis of myelodysplasia and its clinical relevance. Blood 2013,122, 4021–4034.
7. Papaemmanuil, E. et al.; Genomic classification and prognosis in acute myeloid leukemia. N. Engl. J. Med. 2016, 374, 2209–2221.
8. Papaemmanuil, E. et al.; Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood 2013,122, 3616–3627.
9. Abel, H.J., Duncavage, E.J.; Detection of structural DNA variation from next generation sequencing data: a review of nformatics approaches, Cancer Genetics, 206,432- 440, 2013, ISSN 2210-7762, https://doi.org/10.1016/j.cancergen.2013.11.002.
10. Duncavage, E. J. & Tandon, B.; The utility of next-generation sequencing in diagnosis and monitoring of acute myeloid leukemia and myelodysplastic syndromes. Int. J. Lab. Hematol. 37(Suppl 1), 115–121 (2015).
11. Arber, D. A. et al.; The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 127, 2391–2405 (2016).
12. Dohner, H. et al.; Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 129:424–447(2017)
13. Patel, U., Luthra, R., Medeiros, L.J., Patel, K.P.; Diagnostic, Prognostic, and Predictive Utility of Recurrent Somatic Mutations in Myeloid Neoplasms. Clin Lymphoma Myeloma Leuk. 2017 Jul;17S:S62-S74. doi: 10.1016/j.clml.2017.02.015.
14. Cancer Genome Atlas Research. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N. Engl. J. Med. 368, 2059–2074 (2013).
15. Duncavage, E. J., Abel, H. J., Szankasi, P., Kelley, T. W., & Pfeifer, J. D. (2012). Targeted next generation sequencing of clinically significant gene mutations and translocations in leukemia. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 25(6), 795–804. https://doi.org/10.1038/modpathol.2012.29
16. Yoshida, K. et al.; Frequent pathway mutations of splicing machinery in myelodysplasia. Nature 478: 64–69(2011)
17. Bacher, U., Kohlmann, A. & Haferlach, T.; Mutational profiling in patients with MDS: ready for every-day use in the clinic? Best. Pract. Res. Clin. Haematol. 28,32–42 (2015)
18. A Sample to Insight®NGS solution for myeloid neoplasms: Redefined amplicon sequencing for low variant detection and interpretation (Application Note: PROM-12533- 001)(2018)
19. Howe, B., Umrigar, A., Tsien, F.; Chromosome Preparation From Cultured Cells. J. Vis. Exp. (83), e50203, doi:10.3791/50203 (2014).
20. Rack, K.A. et al.; European recommendations and quality assurance for cytogenomic analysis of haematological neoplasms. Leukemia 33, 1851–1867 (2019) doi:10.1038/s41375-019-0378-z
21. Gazzola, A. et al.; The evolution of clonality testing in the diagnosis and monitoring of hematological malignancies. Therapeutic Adv Hematol. (2014) 5:35– 47. doi:10.1177/2040620713519729
22. De Braekeleer, E., Douet-Guilbert, N., & De Braekeleer,M.; Genetic diagnosis in malignant hemopathies: from cytogenetics to next-generation sequencing, Expert Review of Molecular Diagnostics, 2014, 14:2, 127-129, DOI:10.1586/14737159.2014.872563
23. Mitelman, F., Johansson, B., Mertens, F., editors. Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer. 2013. Available from: http://cgap.nci.nih.gov/Chromosomes/Mitelman
24. Kim, H., Yun, J.W., Lee, S.T., Kim, H.J., Kim, S.H., Kim, J.W.; Korean Society for Genetic Diagnostics Clinical Guidelines Committee. Korean Society for Genetic Diagnostics Guidelines for Validation of Next-Generation Sequencing-Based Somatic Variant Detection in Hematologic Malignancies. Ann Lab Med. 2019 Nov;39(6):515-523. doi:10.3343/alm.2019.39.6.515.
25. Avila, M., Bernstam, M.; Next-Generation Sequencing for the General Cancer Patient. Clin Adv Hematol Oncol. 2019,17(8):447-454.
26. National Comprehensive Cancer Network. Myeloproliferative neoplasms (Version 2.2018). Available from: https://www.nccn.org/professsionals/physician_gls/pdf/mpn.pdf.Accessed September 7, 2017.
27. Kuo, F.C., Steensma, D.P., Dal Cin, P.; Conventional cytogenetics for myeloid neoplasms in the era of next generation sequencing. AmJHematol. 2017;92:227229. https://doi.org/10.1002/ajh.24642
28. Delic, S., Rose, D., Kern, W., Nadarajah, N., Haferlach, C., Haferlach, T., Meggendorfer, M.; Application of an NGS-based 28-gene panel in myeloproliferative neoplasms reveals distinct mutation patterns in essential thrombocythaemia, primary myelofibrosis and polycythaemia vera. Br J Haematol. 2016 Nov;175(3):419-426. doi: 10.1111/bjh.14269. Epub 2016 Jul 22.
29. Maes, B., Willemse, J., Broekmans, A., Smets, R., Cruys, B., Put, N., Madoe, V., Janssen, M., Soepenberg, O., Bries, G., Vrelust, I., Achten, R., Van Pelt, K., Buvé, K., Theunissen, K., Peeters, V., & Froyen, G. Targeted next-generation sequencing using a multigene panel in myeloid neoplasms: Implementation in clinical diagnostics. Int J Lab Hematol. 2017;39(6):604-612. doi:10.1111/ijlh.12709.
30. Northrup, V., Maybank, A., Carson, N., Rahmeh, T.; The Value of Next-Generation Sequencing in the Screening and Evaluation of Hematologic Neoplasms in Clinical Practice. Am J Clin Pathol. 2020;153(5):639-645. doi:10.1093/ajcp/aqz203.
31. Kawata, E., Lazo?Langner, A., Xenocostas, A., Hsia, C.C., Howson?Jan, K., Deotare, U., Saini, L., Yang, P., Broadbent, R., Levy, M., Howlett, C., Stuart, A., Kerkhof, J., Santos, S., Lin, H., Sadikovic, B. and Chin?Yee, I. (2020), Clinical value of next?generation sequencing compared to cytogenetics in patients with suspected myelodysplastic syndrome. Br J Haematol. doi:10.1111/bjh.16891
32. Haferlach, T., Nagata, Y., Grossmann, V., Okuno, Y., Bacher, U., Nagae, G., et al.; Landscape of genetic lesions in 944 patients with myelodysplastic syndromes. Leukemia. 2014;28:241–7.
33. Yu, J., Li, Y., Li, T., Li, Y., Xing, H., Sun, H., Sun, L., Wan, D., Liu, Y., Xie, X., & Jiang, Z. (2020). Gene mutational analysis by NGS and its clinical significance in patients with myelodysplastic syndrome and acute myeloid leukemia. Experimental hematology & oncology, 9, 2.
34. Vantyghem, S., Peterlin, P., Thépot, S., Ménard, A., Dubruille, V., Debord, C., Guillaume, T., Garnier, A., Le Bourgeois, A., Wuilleme, S., Godon, C., Theisen, O., Eveillard, M., Delaunay, J., Maisonneuve, H., Morineau, N., Villemagne, B., Vigouroux, S., Subiger, F., Lestang, E., … Le Bris, Y. (2020). Diagnosis and prognosis are comforted by integrated assessment of next-generation sequencing in chronic myeloid malignancies. A real-life study. Haematologica, haematol.2019.242677. Advance online publication. https://doi.org/10.3324/haematol.2019.242677
35. Reinig, E., Yang, F., Traer, E., Arora, R., Brown, S., Rattray, R., Braziel, R., Fan, G., Press, R., & Dunlap, J. (2016). Targeted Next-Generation Sequencing in Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia Aids Diagnosis in Challenging Cases and Identifies Frequent Spliceosome Mutations in Transformed Acute Myeloid Leukemia. American journal of clinical pathology, 145(4), 497–506. https://doi.org/10.1093/ajcp/aqw016
36. Levy, M.A., Santos, S., Kerkhof, J., et al.; Implementation of an NGS-based sequencing and gene fusion panel for clinical screening of patients with suspected hematologic malignancies. Eur J Haematol. 2019;103(3):178-189. doi:10.1111/ejh.13272.
37. Yun, S., Geyer, S. M., Komrokji, R. S., Al Ali, N. H., Song, J., Hussaini, M., Sweet, K. L., Lancet, J. E., List, A. F., Padron, E., & Sallman, D. A. (2020). Prognostic significance of serial molecular annotation in myelodysplastic syndromes (MDS) and secondary acute myeloid leukemia (sAML). Leukemia, 10.1038/s41375-020-0997-4. Advance online publication. https://doi.org/10.1038/s41375-020-0997-4
Article Sidebar
Article Details
How to Cite
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Transfer of Copyright and Permission to Reproduce Parts of Published Papers. Authors will grant copyright of their articles to the Institute of Hematology, Catholic University, Rome . No formal permission will be required to reproduce parts (tables or illustrations) of published papers, provided the source is quoted appropriately and reproduction has no commercial intent. Reproductions with commercial intent will require written permission and payment of royalties.