PTPN11, RAS and FLT3 mutations in childhood acute lymphoblastic leukemia.
PTPN11, the gene which encodes protein tyrosine phosphatase SHP-2, plays an important role in regulating intracellular signaling. Germline mutations in PTPN11 were first observed in Noonan syndrome, while somatic mutations were identified in hematological myeloid malignancies. Recently, PTPN11 mutations have been reported in children with acute lymphoblastic leukemia (ALL). In the present study, we investigated the prevalence of mutations in PTPN11, RAS and FLT3 in samples from 95 Japanese children with ALL. We observed exon 3 and 8 missense mutations of PTPN11 in 6 children with B precursor ALL. One patient with Down syndrome and ALL had PTPN11 mutation. We also identified RAS mutations in ten patients and FLT3 internal tandem duplication (FLT3/ITD) in one patient. None of the patients had simultaneous mutations in PTPN11 and RAS, while one patient had both PTPN11 and FLT3 mutations. These data suggest that PTPN11 mutation may play an important role for leukemogenesis in a proportion of children with ALL, particularly B precursor ALL.
Departments of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan. tomotomo@med.nagoya-u.ac.jp
Tomoko
T
Yamamoto
Mariko
M
Isomura
Yinyan
Y
Xu
Juan
J
Liang
Hiroshi
H
Yagasaki
Yoshiro
Y
Kamachi
Kazuko
K
Kudo
Hitoshi
H
Kiyoi
Tomoki
T
Naoe
Seiji
S
Kojma
D000293:Adolescent; D002051:Burkitt Lymphoma / Q000150:complications / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004314:Down Syndrome / Q000150:complications / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D007564:Japan; D008297:Male; D020125:Mutation, Missense; D009634:Noonan Syndrome / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000235:genetics*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*; D018631:ras Proteins / Q000235:genetics*
D047908:Intracellular Signaling Peptides and Proteins; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases; D018631:ras Proteins