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FISH analysis for TET2 deletion in a cohort of 362 Brazilian myeloid malignancies: correlation with karyotype abnormalities

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Abstract

We investigated the prevalence of TET2 deletion by using a new FISH probe in a cohort of 362 Brazilian patients with myeloid neoplasms and their association with cytogenetic information (G-banding analysis). Normal karyotype was observed in 45.8 % of MDS (n = 44), 43.8 % of AML (n = 39) and 46.3 % of MPN (n = 82). Abnormalities of 4q24 (deletions, translocations or inversions) were associated with another chromosomal abnormality in four patients by G-banding analysis (2 MDS, 1 AML and 1 MPN). Interphase FISH analysis revealed deletion of TET2 in 21 patients (6 patients with abnormal karyotype and in 15 patients with normal karyotype). arrayCGH analysis revealed a cryptic deletion of the region 4q24 in all eight patients selected with myeloid malignancies (3 MDS, 1 AML and 4 MPN). Considering the significantly high cost of determining the mutational status of TET2 in patient samples by using conventional sequencing methods and sometimes the lack of regular use of SNP/aCGH array methodologies, FISH for the detection of TET2 abnormalities may become a potentially useful clinical tool. The search for alterations in TET2 gene may be important for the prediction of prognosis in normal/altered AML patients’ karyotype or in the disease evolution of patients with MNP and MDS.

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References

  1. Abdel-Wahab O, Mullally A, Hedvat C, Garcia-Manero G, et al. Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies. Blood. 2009;114(1):144–7.

    Article  PubMed  CAS  Google Scholar 

  2. Delhommeau F, Dupont S, Della Valle V, et al. Mutation in TET2 in myeloid cancers. N Engl J Med. 2009;360(22):2289–301.

    Article  PubMed  Google Scholar 

  3. Moran-Crusio K, Reavie L, Shih A, et al. TET2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation. Cancer Cell. 2011;20(1):11–24.

    Article  PubMed  CAS  Google Scholar 

  4. Abdel-Wahab O, Manshouri T, Patel J, et al. Genetic analysis of transforming events that convert chronic myeloproliferative neoplasms to leukemias. Cancer Res. 2010;70(2):447–52.

    Article  PubMed  CAS  Google Scholar 

  5. Quivoron C, Couronné L, Della Valle V, et al. TET2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis. Cancer Cell. 2011;20(1):25–38.

    Article  PubMed  CAS  Google Scholar 

  6. La Starza R, Crescenzi B, Nofrini V, et al. FISH analysis reveals frequent co-occurrence of 4q24/TET2 and 5q and/or 7q deletions. Leuk Res. 2012;36(1):37–41.

    Article  PubMed  Google Scholar 

  7. Pronier E, Delhommeau F. Role of TET2 mutations in myeloproliferative neoplasms. Curr Hematol Malig Rep. 2012;7(1):57–64.

    Article  PubMed  Google Scholar 

  8. Tripodi J, Hoffman R, Najfeld V, Weinberg R. Frequency of heterozygous TET2 deletions in myeloproliferative neoplasms. Cancer Manag Res. 2010;2:219–23.

    PubMed  CAS  Google Scholar 

  9. Metzeler KH, Maharry K, Radmacher MD, et al. TET2 mutations improve the new European LeukemiaNet risk classification of acute myeloid leukemia: a cancer and leukemia group b study. J Clin Oncol. 2011;29(10):1373–81.

    Article  PubMed  Google Scholar 

  10. Makishima H, Jankowska AM, McDevitt MA, et al. CBL, CBLB, TET2, ASXL1, and IDH1/2 mutations and additional chromosomal aberrations constitute molecular events in chronic myelogenous leukemia. Blood. 2011;117(21):198–206.

    Article  Google Scholar 

  11. Roche-Lestienne C, Marceau A, Labis E, et al. Mutation analysis of TET2, IDH1, IDH2 and ASXL1 in chronic myeloid leukemia. Leukemia. 2011;25(10):1661–4.

    Article  PubMed  CAS  Google Scholar 

  12. Pignataro DS, Abdel-Wahab O. FISHing for TET2: utility of FISH for TET2 deletions detection in clinical samples. Leuk Res. 2012;36(1):25–6.

    Article  PubMed  Google Scholar 

  13. Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood. 2002;100(7):2292–302.

    Article  PubMed  CAS  Google Scholar 

  14. Morato de Oliveira F, Lucena-Araujo AR, Favarin MD, et al. Differential expression of AURKA and AURKB genes in bone marrow stromal mesenchymal cells of myelodisplastic syndrome: correlation with G-banding analysis and FISH. Exp Hematol. 2012. doi:10.1016/j.exphem.2012.10.009 (Epub ahead of print).

  15. Shaffer LG, Slovak ML, Campbell LJ, editors. ISCN 2009: an international system for human cytogenetic nomenclature 2009. Basel: S. Karger; 2009.

    Google Scholar 

  16. Starczynowski DT, Vercauteren S, Telenius A, et al. High-resolution whole genome tiling path array CGH analysis of CD34 + cells from patients with low-risk myelodysplastic syndromes reveals cryptic copy number alterations and predicts overall and leukemia-free survival. Blood. 2008;112(8):3412–24.

    Article  PubMed  CAS  Google Scholar 

  17. Bacher U, Weissmann S, Kohlmann A, et al. TET2 deletions are a recurrent but rare phenomenon in myeloid malignancies and are frequently accompanied by TET2 mutations on the remaining allele. Br J Haematol. 2012;156(1):67–75.

    Article  PubMed  Google Scholar 

  18. Kohlmann A, Grossmann V, Klein HU, et al. Next-generation sequencing technology reveals a characteristic pattern of molecular mutations in 72.8% of chronic myelomonocytic leukemia by detecting frequent alterations in TET2, CBL, RAS, and RUNX1. J Clin Oncol. 2010;28(24):3858–65.

    Article  PubMed  CAS  Google Scholar 

  19. Schaub FX, Looser R, Li S, et al. Clonal analysis of TET2 and JAK2 mutations suggests that TET2 can be a late event in the progression of myeloproliferative neoplasms. Blood. 2010;115(10):2003–7.

    Article  PubMed  CAS  Google Scholar 

  20. Saint-Martin C, Leroy G, Delhommeau F, et al. Analysis of the ten-eleven translocation 2 (TET2) gene in familial myeloproliferative neoplasms. Blood. 2009;114(8):1628–32.

    Article  PubMed  CAS  Google Scholar 

  21. Kosmider O, Gelsi-Boyer V, Ciudad M, et al. TET2 gene mutation is a frequent and adverse event in chronic myelomonocytic leukemia. Haematologica. 2009;94(12):1676–81.

    Article  PubMed  CAS  Google Scholar 

  22. Kosmider O, Gelsi-Boyer V, Cheok M, et al. TET2 mutation is an independent favorable prognostic factor in myelodysplastic syndromes (MDSs). Blood. 2009;114(15):3285–91.

    Article  PubMed  CAS  Google Scholar 

  23. Nibourel O, Kosmider O, Cheok M, et al. Incidence and prognostic value of TET2 alterations in de novo acute myeloid leukemia achieving complete remission. Blood. 2010;116(7):1132–5.

    Article  PubMed  CAS  Google Scholar 

  24. Brecqueville M, Rey J, Bertucci F, et al. Mutation analysis of ASXL1, CBL, DNMT3A, IDH1, IDH2, JAK2, MPL, NF1, SF3B1, SUZ12, and TET2 in myeloproliferative neoplasms. Genes Chromosom Cancer. 2012;51:743–55.

    Article  PubMed  CAS  Google Scholar 

  25. Tefferi A, Lim KH, Abdel-Wahab O, et al. Detection of mutant TET2 in myeloid malignancies other than myeloproliferative neoplasms: CMML, MDS MDS/MPN and AML. Leukemia. 2009;23(7):1343–5.

    Article  PubMed  CAS  Google Scholar 

  26. Tefferi A, Pardanani A, Lim KH, et al. TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis. Leukemia. 2009;23(5):905–11.

    Article  PubMed  CAS  Google Scholar 

  27. Zamora L, Xandri M, Garcia O, et al. Association of JAK2 mutation status and cytogenetic abnormalities at diagnosis in myeloproliferative neoplasms and myelodysplastic/myeloproliferative neoplasms. Am J Clin Pathol. 2012;137(4):677–8.

    Article  PubMed  Google Scholar 

  28. Bejar R, Levine R, Ebert BL. Unraveling the molecular pathophysiology of myelodysplastic syndromes. J Clin Oncol. 2011;29(5):504–15.

    Article  PubMed  CAS  Google Scholar 

  29. Falini B, Martelli MP. NPM1-mutated AML: targeting by disassembling. Blood. 2011;118(11):2936–8.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This investigation was supported by FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo) (2011/01647-2) and the National Institute of Science and Technology in Stem Cell and Cell Therapy, Ribeirão Preto, Brazil (Proc. 52462-7/2007-0).

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All the authors reported no potential conflicts of interest.

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Correspondence to Fábio Morato de Oliveira.

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de Oliveira, F.M., Miguel, C.E., Lucena-Araujo, A.R. et al. FISH analysis for TET2 deletion in a cohort of 362 Brazilian myeloid malignancies: correlation with karyotype abnormalities. Med Oncol 30, 483 (2013). https://doi.org/10.1007/s12032-013-0483-1

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  • DOI: https://doi.org/10.1007/s12032-013-0483-1

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