title: Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia.
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.
authors.affiliation: Department of Pediatrics, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Tartaglia
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Niemeyer
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fragale
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Song
authors.forename: Jochen
authors.initials: J
authors.lastname: Buechner
authors.forename: Andreas
authors.initials: A
authors.lastname: Jung
authors.forename: Karel
authors.initials: K
authors.lastname: Hählen
authors.forename: Henrik
authors.initials: H
authors.lastname: Hasle
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Licht
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Gelb
mesh_terms: D000818:Animals; D019556:COS Cells; D002648:Child; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology* / Q000235:genetics*; D015479:Leukemia, Myelomonocytic, Acute / Q000150:complications / Q000201:enzymology* / Q000235:genetics*; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000201:enzymology* / Q000235:genetics*; D009634:Noonan Syndrome / Q000150:complications / Q000201:enzymology / Q000235:genetics; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases