title: The mutational spectrum of PTPN11 in juvenile myelomonocytic leukemia and Noonan syndrome/myeloproliferative disease.
abstract: Germ line PTPN11 mutations cause 50% of cases of Noonan syndrome (NS). Somatic mutations in PTPN11 occur in 35% of patients with de novo, nonsyndromic juvenile myelomonocytic leukemia (JMML). Myeloproliferative disorders (MPDs), either transient or more fulminant forms, can also occur in infants with NS (NS/MPD). We identified PTPN11 mutations in blood or bone marrow specimens from 77 newly reported patients with JMML (n = 69) or NS/MPD (n = 8). Together with previous reports, we compared the spectrum of PTPN11 mutations in 3 groups: (1) patients with JMML (n = 107); (2) patients with NS/MPD (n = 19); and (3) patients with NS (n = 243). Glu76 was the most commonly affected residue in JMML (n = 45), with the Glu76Lys alteration (n = 29) being most frequent. Eight of 19 patients with NS/MPD carried the Thr73Ile substitution. These data suggest that there is a genotype/phenotype correlation in the spectrum of PTPN11 mutations found in patients with JMML, NS/MPD, and NS. This supports the need to characterize the spectrum of hematologic abnormalities in individuals with NS and to better define the impact of the PTPN11 lesion on the disease course in patients with NS/MPD and JMML.
authors.affiliation: University of California, Room HSE-302 Box 0519, San Francisco, CA 94143, USA.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Kratz
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Niemeyer
authors.forename: Robert P
authors.initials: RP
authors.lastname: Castleberry
authors.forename: Mualla
authors.initials: M
authors.lastname: Cetin
authors.forename: Eva
authors.initials: E
authors.lastname: Bergsträsser
authors.forename: Peter D
authors.initials: PD
authors.lastname: Emanuel
authors.forename: Henrik
authors.initials: H
authors.lastname: Hasle
authors.forename: Gabriela
authors.initials: G
authors.lastname: Kardos
authors.forename: Cornelia
authors.initials: C
authors.lastname: Klein
authors.forename: Seiji
authors.initials: S
authors.lastname: Kojima
authors.forename: Jan
authors.initials: J
authors.lastname: Stary
authors.forename: Monika
authors.initials: M
authors.lastname: Trebo
authors.forename: Marco
authors.initials: M
authors.lastname: Zecca
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Gelb
authors.forename: Marco
authors.initials: M
authors.lastname: Tartaglia
authors.forename: Mignon L
authors.initials: ML
authors.lastname: Loh
mesh_terms: D002648:Child; D004252:DNA Mutational Analysis; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D015477:Leukemia, Myelomonocytic, Chronic / Q000235:genetics*; D009154:Mutation; D020125:Mutation, Missense; D009196:Myeloproliferative Disorders / Q000235:genetics*; D009634:Noonan Syndrome / Q000235:genetics*; D010641:Phenotype; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases