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Leukemia. 2020 Feb 17. doi: 10.1038/s41375-020-0728-x. [Epub ahead of print]

Impact of somatic mutations in myelodysplastic patients with isolated partial or total loss of chromosome 7.

Author information

1
Department of Haematological Medicine, King's College Hospital, NHS Foundation Trust, London, UK. elena.crisa@med.uniupo.it.
2
Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy. elena.crisa@med.uniupo.it.
3
Fondazione Italiana Sindromi Mielodisplastiche (FISiM), Bologna, Italy. elena.crisa@med.uniupo.it.
4
Department of Haematological Medicine, King's College Hospital, NHS Foundation Trust, London, UK.
5
Institut de Recerca Contra la Leucèmia Josep Carreras, ICO-Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain.
6
Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
7
Department of Hematology, Hospital Universitario La Fe, Valencia, Spain.
8
Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain.
9
Department of Hematology and Medical Oncology, University Medical Center of Göttingen, Göttingen, Germany.
10
Laboratory for Molecular Haemato-Oncology, King's College Hospital, NHS Foundation Trust, London, UK.
11
Haematopoietic Stem Cell Laboratory, The Francis Crick Institute, London, UK.
12
Genetics Unit, Hospital Universitario La Fe, Valencia, Spain.
13
Fondazione Italiana Sindromi Mielodisplastiche (FISiM), Bologna, Italy.
14
Division of Hematology, University of Torino, AOU Città della Salute e della Scienza, Torino, Italy.
15
Department of Hematology, Oncology, and Clinical Immunology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
16
Institute of Human Genetics, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
17
MDS UNIT, AOU Careggi, University of Florence, Firenze, Italy.
18
Department of Medicine, University of Valencia, Valencia, Spain.

Abstract

Monosomy 7 [-7] and/or partial loss of chromosome 7 [del(7q)] are associated with poor and intermediate prognosis, respectively, in myelodysplastic syndromes (MDS), but somatic mutations may also play a key complementary role. We analyzed the impact on the outcomes of deep targeted mutational screening in 280 MDS patients with -7/del(7q) as isolated cytogenetic abnormality (86 with del(7q) and 194 with -7). Patients with del(7q) or -7 had similar demographic and disease-related characteristics. Somatic mutations were detected in 79% (93/117) of patients (82% in -7 and 73% in del(7q) group). Median number of mutations per patient was 2 (range 0-8). There was no difference in mutation frequency between the two groups. Patients harbouring ≥2 mutations had a worse outcome than patients with <2 or no mutations (leukaemic transformation at 24 months, 38% and 20%, respectively, p = 0.044). Untreated patients with del(7q) had better overall survival (OS) compared with -7 (median OS, 34 vs 17 months, p = 0.034). In multivariable analysis, blast count, TP53 mutations and number of mutations were independent predictors of OS, whereas the cytogenetic subgroups did not retain prognostic relevance. This study highlights the importance of mutational analysis in terms of prognosis in MDS patients with isolated -7 or del(7q).

PMID:
32066866
DOI:
10.1038/s41375-020-0728-x

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