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Blood, 15 September 2005, Vol. 106, No. 6, pp. 2183-2185.
Prepublished online as a Blood First Edition Paper on May 31, 2005; DOI 10.1182/blood-2005-02-0531.
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NEOPLASIA
Brief report
The mutational spectrum of PTPN11 in juvenile myelomonocytic leukemia and Noonan syndrome/myeloproliferative disease
Christian P. Kratz,
Charlotte M. Niemeyer,
Robert P. Castleberry,
Mualla Cetin,
Eva Bergsträsser,
Peter D. Emanuel,
Henrik Hasle,
Gabriela Kardos,
Cornelia Klein,
Seiji Kojima,
Jan Stary,
Monika Trebo,
Marco Zecca,
Bruce D. Gelb,
Marco Tartaglia, and
Mignon L. Loh
From the Department of Pediatrics and Adolescent Medicine, University of Freiburg, Germany; Department of Pediatric Hematology/Oncology and Division of Hematology/Oncology, Comprehensive Cancer Center, University of Alabama at Birmingham, AL; Department of Pediatric Hematology, Ihsan Dogramaci Children's Hospital, Hacettepe University, Ankara, Turkey; Department of Pediatrics, Zurich, Switzerland; Department of Pediatrics, Skejby Hospital, Aarhus University, Denmark; Dutch Childhood Oncology Group, the Hague, the Netherlands; Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan; Department of Pediatrics, University Hospital Motol, Prague, Czech Republic; St Anna Children's Hospital, Vienna, Austria; Oncoematologia Pediatrica, Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy; Departments of Pediatrics and Human Genetics, Mount Sinai School of Medicine, New York, NY; Dipartimento di Biologia Cellulare e Neuroscienze, Instituto Superiore di Sanità, Rome, Italy; and Department of Pediatrics and the Comprehensive Cancer Center, University of California at San Francisco, CA.
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)
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