Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia.
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.
Tartaglia
Marco
M
Department of Pediatrics, Mount Sinai School of Medicine, New York, New York, USA.
Niemeyer
Charlotte M
CM
Fragale
Alessandra
A
Song
Xiaoling
X
Buechner
Jochen
J
Jung
Andreas
A
Hählen
Karel
K
Hasle
Henrik
H
Licht
Jonathan D
JD
Gelb
Bruce D
BD
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
D047908:Intracellular Signaling Peptides and Proteins; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases