The mutational spectrum of PTPN11 in juvenile myelomonocytic leukemia and Noonan syndrome/myeloproliferative disease

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 wit...

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Bibliographic Details
Published in:Blood 2005-09, Vol.106 (6), p.2183-2185
Main Authors: Kratz, Christian P., Niemeyer, Charlotte M., Castleberry, Robert P., Cetin, Mualla, Bergsträsser, Eva, Emanuel, Peter D., Hasle, Henrik, Kardos, Gabriela, Klein, Cornelia, Kojima, Seiji, Stary, Jan, Trebo, Monika, Zecca, Marco, Gelb, Bruce D., Tartaglia, Marco, Loh, Mignon L.
Format: Article
Language:English
Subjects:
Biological and medical sciences
Child
Diseases of the osteoarticular system
DNA Mutational Analysis
Hematologic and hematopoietic diseases
Humans
Intracellular Signaling Peptides and Proteins - genetics
Leukemia, Myelomonocytic, Chronic - genetics
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Malformations and congenital and or hereditary diseases involving bones. Joint deformations
Medical sciences
Mutation
Mutation, Missense
Myeloproliferative Disorders - genetics
Neoplasia
Noonan Syndrome - genetics
Phenotype
Protein Tyrosine Phosphatase, Non-Receptor Type 11
Protein Tyrosine Phosphatases - genetics
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Description
Summary: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. (Blood. 2005;106:2183-2185)
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2005-02-0531