Germline GATA2 mutations cause cellular deficiencies with high propensity for myeloid disease. We investigated 426 children and adolescents with primary myelodysplastic syndrome (MDS) and 82 cases with secondary MDS enrolled in 2 consecutive prospective studies of the European Working Group of MDS in Childhood (EWOG-MDS) conducted in Germany over a period of 15 years. Germline GATA2 mutations accounted for 15% of advanced and 7% of all primary MDS cases, but were absent in children with MDS secondary to therapy or acquired aplastic anemia. Mutation carriers were older at diagnosis and more likely to present with monosomy 7 and advanced disease compared with wild-type cases. For stratified analysis according to karyotype, 108 additional primary MDS patients registered with EWOG-MDS were studied. Overall, we identified 57 MDS patients with germline GATA2 mutations. GATA2 mutations were highly prevalent among patients with monosomy 7 (37%, all ages) reaching its peak in adolescence (72% of adolescents with monosomy 7). Unexpectedly, monocytosis was more frequent in GATA2-mutated patients. However, when adjusted for the selection bias from monosomy 7, mutational status had no effect on the hematologic phenotype. Finally, overall survival and outcome of hematopoietic stem cell transplantation (HSCT) were not influenced by mutational status. This study identifies GATA2 mutations as the most common germline defect predisposing to pediatric MDS with a very high prevalence in adolescents with monosomy 7. GATA2 mutations do not confer poor prognosis in childhood MDS. However, the high risk for progression to advanced disease must guide decision-making toward timely HSCT.

Department of Hematology and Oncology Hospital Sant Joan de Déu Barcelona Spain

Department of Hematology and Oncology University Children's Hospital Zurich Switzerland

Department of Pathology Clinical Center Böblingen Germany

Department of Pediatric Hematology and Oncology Bambino Gesù Children's Hospital Rome University of Pavia Pavia Italy

Department of Pediatric Hematology and Oncology Charles University and University Hospital Motol Prague Czech Republic

Department of Pediatric Hematology and Oncology Dr v Hauner Children's Hospital Ludwig Maximilians University Munich Germany

Department of Pediatric Hematology Oncology and BMT Medical University of Wroclaw Wroclaw Poland

Department of Pediatric Hematology Oncology and Stem Cell Transplantation Ghent University Hospital Ghent Belgium

Department of Pediatric Oncology and Hematology University of Bologna Bologna Italy

Department of Pediatrics Aarhus University Hospital Skejby Aarhus Denmark

Department of Pediatrics Leiden University Medical Center Leiden The Netherlands

Division of Pediatric Hematology and Oncology Department of Pediatrics and Adolescent Medicine University of Freiburg Freiburg Germany

Erasmus Medical Center Rotterdam and Dutch Childhood Oncology Group The Hague The Netherlands

German Cancer Consortium Freiburg Germany and German Cancer Research Center Heidelberg Germany

Institute of Human Genetics Hannover Medical School Hannover Germany

Institute of Pathology University of Erlangen Erlangen Germany

Paediatric Oncology and Haematology Our Lady's Children's Hospital Crumlin Dublin Ireland

Pediatric Hematology and Oncology Hannover Medical School Hannover Germany

Pediatric Hematology Oncology Fondazione Istituti di ricovero e cura a carattere scientifico Policlinico San Matteo Pavia Italy

Pediatric Oncology Charité University Medicine Berlin Berlin Germany

Pediatric Oncology Queen Silvias Children's Hospital Gothenburg Sweden

St Anna Children's Hospital and Children's Cancer Research Institute Medical University of Vienna Vienna Austria

Taussig Cancer Institute Cleveland Clinic Cleveland OH

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