Abstract
We report here that individuals with Noonan syndrome and juvenile myelomonocytic leukemia (JMML) have germline mutations in PTPN11 and that somatic mutations in PTPN11 account for 34% of non-syndromic JMML. Furthermore, we found mutations in PTPN11 in a small percentage of individuals with myelodysplastic syndrome (MDS) and de novo acute myeloid leukemia (AML). Functional analyses documented that the two most common mutations in PTPN11 associated with JMML caused a gain of function.
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Acknowledgements
We thank the affected individuals and their families who participated in the study, the physicians who referred the subjects, I. Baumann for reference morphology review, J. Harbott for cytogenetic studies, S. Lassmann for DNA extraction from tissue samples, F. Lecaill for assistance in preparing graphical representation of the SHP-2 mutations and A. Fisher and P. Noellke for statistical analysis. This work was supported in part by grants from Mount Sinai Children's Health Research Center and National Institutes of Health to B.D.G., Progetto di ricerca finalizzata 1% FSN 2002 “Valutazione molecolare e funzionale delle malformazioni e disfunzioni cardiache su base genetica” to M.T. and Deusche José Carreras Leukämie-Stiftung e.V. and Bundesministerium fuer Bildung und Forschung Competence Network: Pediatric Oncology (Project E: Preleukemic Bone Marrow Disorders) to C.M.N.
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M.T. and B.D.G. have a patent application pending concerning mutations in PTPN11 and Noonan syndrome. M.T., C.M.N. and B.D.G. have a patent application pending concerning mutations in PTPN11 and myeloid disorders.
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Tartaglia, M., Niemeyer, C., Fragale, A. et al. Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia. Nat Genet 34, 148–150 (2003). https://doi.org/10.1038/ng1156
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DOI: https://doi.org/10.1038/ng1156
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