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Genomic characterization and prognostication applied to a Brazilian cohort of patients with myelofibrosis

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Abstract

Genomic characterization of patients with myeloproliferative neoplasms (MPN) may lead to better diagnostic classification, prognostic assessment, and treatment decisions. These goals are particularly important in myelofibrosis (MF). We performed target Next Generation Sequencing for a panel of 255 genes and Chromosome Microarray Analysis (CMA) in 27 patients with MF. Patients were classified according to genomic findings and we compared the performance of a personalized prognostication system with IPSS, MIPSS70 and MIPSS70 + v2. Twenty-six patients presented mutations: 11.1% had single driver mutations in either JAK2, CALR or MPL; 85.2% had mutations in non-restricted genes (median: 2 per patient). CMA was abnormal in 91.7% of the 24 cases with available data. Copy-Number-Neutral Loss-of-Heterozygosity was the most common finding (66.7%). Del13q was the most frequent copy number variation, and we could define a 2.4 Mb minimally affected region encompassing RB1, SUCLA2 and CLLS2 loci. The largest genomic subgroup consisted of patients with mutations in genes involved with chromatin organization and splicing control (40.7%) and the personalized system showed better concordance and accuracy than the other prognostic systems. Comprehensive genomic characterization reveals the striking genetic complexity of MF and, when combined with clinical data, led, in our cohort, to better prognostication performance.

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Authors and Affiliations

  1. Secretaria de Saude do Distrito Federal, Brasilia, Brazil

    Alexandre Nonino

  2. Cettro – Centro de Cancer de Brasilia, Brasilia, Brazil

    Alexandre Nonino

  3. Hospital Israelita Albert Einstein, São Paulo, Brazil

    Paulo Vidal Campregher & Fabio Pires de Souza Santos

  4. Faculdade de Medicina da Universidade de Brasilia, Brasilia, Brazil

    Juliana Forte Mazzeu

  5. Escola de Saude e Medicina da Universidade Catolica de Brasilia, Brasilia, Brazil

    Rinaldo Wellerson Pereira

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  1. Alexandre Nonino
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Correspondence to Alexandre Nonino.

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Supplementary file1 (DOCX 23 kb) NGS Protocol and Table S1. NGS panel

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Nonino, A., Campregher, P.V., de Souza Santos, F.P. et al. Genomic characterization and prognostication applied to a Brazilian cohort of patients with myelofibrosis. Int J Hematol 112, 361–368 (2020). https://doi.org/10.1007/s12185-020-02906-w

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  • DOI: https://doi.org/10.1007/s12185-020-02906-w

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