title: Mutations in CBL occur frequently in juvenile myelomonocytic leukemia.
abstract: Juvenile myelomonocytic leukemia is an aggressive myeloproliferative disorder characterized by malignant transformation in the hematopoietic stem cell compartment with proliferation of differentiated progeny. Seventy-five percent of patients harbor mutations in the NF1, NRAS, KRAS, or PTPN11 genes, which encode components of Ras signaling networks. Using single nucleotide polymorphism arrays, we identified a region of 11q isodisomy that contains the CBL gene in several JMML samples, and subsequently identified CBL mutations in 27 of 159 JMML samples. Thirteen of these mutations alter codon Y371. In this report, we also demonstrate that CBL and RAS/PTPN11 mutations were mutually exclusive in these patients. Moreover, the exclusivity of CBL mutations with respect to other Ras pathway-associated mutations indicates that CBL may have a role in deregulating this key pathway in JMML.
authors: Department of Pediatrics and the Comprehensive Cancer Center, University of California, San Francisco, California, USA. lohm@peds.ucsf.edu
authors: Mignon L
authors: ML
authors: Loh
authors: Debbie S
authors: DS
authors: Sakai
authors: Christian
authors: C
authors: Flotho
authors: Michelle
authors: M
authors: Kang
authors: Manfred
authors: M
authors: Fliegauf
authors: Sophie
authors: S
authors: Archambeault
authors: Charles G
authors: CG
authors: Mullighan
authors: Leslie
authors: L
authors: Chen
authors: Eva
authors: E
authors: Bergstraesser
authors: Carlos E
authors: CE
authors: Bueso-Ramos
authors: Peter D
authors: PD
authors: Emanuel
authors: Henrik
authors: H
authors: Hasle
authors: Jean-Pierre
authors: JP
authors: Issa
authors: Marry M
authors: MM
authors: van den Heuvel-Eibrink
authors: Franco
authors: F
authors: Locatelli
authors: Jan
authors: J
authors: Stary
authors: Monica
authors: M
authors: Trebo
authors: Marcin
authors: M
authors: Wlodarski
authors: Marco
authors: M
authors: Zecca
authors: Kevin M
authors: KM
authors: Shannon
authors: Charlotte M
authors: CM
authors: Niemeyer
mesh_terms: D002648:Child; D002675:Child, Preschool; D003062:Codon; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006720:Homozygote; D006801:Humans; D007223:Infant; D054429:Leukemia, Myelomonocytic, Juvenile / Q000235:genetics*; D019656:Loss of Heterozygosity; D008297:Male; D009154:Mutation; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D003062:Codon; D050721:Proto-Oncogene Proteins c-cbl; C067419:CBL protein, human