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

Fecha de publicación: 01/09/2020 Fecha Ahead of Print: 17/02/2020

Autores de IIS La Fe

Esperanza Such Taboada

Autor
José Vicente Cervera Zamora

Autor

Participantes ajenos a IIS La Fe

Crisà E
Kulasekararaj AG
Adema V
Schanz J
Haase D
Shirneshan K
Best S
Mian SA
Kizilors A
Lea N
Ferrero D
Germing U
Hildebrandt B
Martínez ABV
Santini V
Sanz GF
Solé F
Mufti GJ

Grupos

Hematología y Hemoterapia

Investigador Principal

Javier De La Rubia Comos

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).

Datos de la publicación

ISSN/ISSNe:: 0887-6924, 1476-5551
Tipo:: Article
Páginas:: 2441-2450
DOI:: 10.1038/s41375-020-0728-x
Factor de Impacto:: 4,539 SCImago ℠
Cuartil:: Q1 SCImago ℠

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Métricas

Filiaciones

Crisà E:: Department of Haematological Medicine, King's College Hospital, NHS Foundation Trust, London, UK.

Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy.

Fondazione Italiana Sindromi Mielodisplastiche (FISiM), Bologna, Italy.
Kulasekararaj AG:: Department of Haematological Medicine, King's College Hospital, NHS Foundation Trust, London, UK
Adema V:: Institut de Recerca Contra la Leucèmia Josep Carreras, ICO-Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain

Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA
Such E:: Department of Hematology, Hospital Universitario La Fe, Valencia, Spain

Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain
Schanz J:: Department of Hematology and Medical Oncology, University Medical Center of Göttingen, Göttingen, Germany
Haase D:: Department of Hematology and Medical Oncology, University Medical Center of Göttingen, Göttingen, Germany
Shirneshan K:: Department of Hematology and Medical Oncology, University Medical Center of Göttingen, Göttingen, Germany
Best S:: Laboratory for Molecular Haemato-Oncology, King's College Hospital, NHS Foundation Trust, London, UK
Mian SA:: Department of Haematological Medicine, King's College Hospital, NHS Foundation Trust, London, UK

Haematopoietic Stem Cell Laboratory, The Francis Crick Institute, London, UK
Kizilors A:: Laboratory for Molecular Haemato-Oncology, King's College Hospital, NHS Foundation Trust, London, UK
Cervera J:: Genetics Unit, Hospital Universitario La Fe, Valencia, Spain
Lea N:: Laboratory for Molecular Haemato-Oncology, King's College Hospital, NHS Foundation Trust, London, UK
Ferrero D:: Fondazione Italiana Sindromi Mielodisplastiche (FISiM), Bologna, Italy

Division of Hematology, University of Torino, AOU Città della Salute e della Scienza, Torino, Italy
Germing U:: Department of Hematology, Oncology, and Clinical Immunology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
Hildebrandt B:: Institute of Human Genetics, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
Martínez ABV:: MDS UNIT, AOU Careggi, University of Florence, Firenze, Italy
Santini V:: Fondazione Italiana Sindromi Mielodisplastiche (FISiM), Bologna, Italy

MDS UNIT, AOU Careggi, University of Florence, Firenze, Italy
Sanz GF:: Department of Hematology, Hospital Universitario La Fe, Valencia, Spain

Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain

Department of Medicine, University of Valencia, Valencia, Spain
Solé F:: Institut de Recerca Contra la Leucèmia Josep Carreras, ICO-Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain
Mufti GJ:: Department of Haematological Medicine, King's College Hospital, NHS Foundation Trust, London, UK

Keywords

METHYLTRANSFERASE GENE EZH2; PROGNOSTIC SCORING SYSTEM; BONE-MARROW FIBROSIS; DISORDERS; 7Q; ABNORMALITIES; ASSOCIATIONS; MONOSOMY-7; KARYOTYPE; LEUKEMIA