title: Casitas B-cell lymphoma mutation in childhood T-cell acute lymphoblastic leukemia.
abstract: Somatic CBL mutations have been reported in a variety of myeloid neoplasms but are rare in acute lymphoblastic leukemia (ALL). We analyzed 77 samples from hematologic malignancies, identifying a somatic mutation in CBL (p.C381R) in one patient with T-ALL that was associated with a uniparental disomy at the CBL locus and a germline heterozygous mutation in one patient with JMML. Two NOTCH1 mutations and homozygous deletions in LEF1 and CDKN2A were identified in T-ALL cells. The activation of the RAS pathway was enhanced, and activation of the NOTCH1 pathway was inhibited in NIH 3T3 cells that expressed p.C381R. This study appears to be the first to identify a CBL mutation in T-ALL.
authors.affiliation: Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Saito
authors.forename: Yoko
authors.initials: Y
authors.lastname: Aoki
authors.forename: Hideki
authors.initials: H
authors.lastname: Muramatsu
authors.forename: Hideki
authors.initials: H
authors.lastname: Makishima
authors.forename: Jaroslaw P
authors.initials: JP
authors.lastname: Maciejewski
authors.forename: Masue
authors.initials: M
authors.lastname: Imaizumi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Rikiishi
authors.forename: Yoji
authors.initials: Y
authors.lastname: Sasahara
authors.forename: Shigeo
authors.initials: S
authors.lastname: Kure
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Niihori
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tsuchiya
authors.forename: Seiji
authors.initials: S
authors.lastname: Kojima
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Matsubara
mesh_terms: D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D002648:Child; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007223:Infant; D008297:Male; D051379:Mice; D009154:Mutation / Q000502:physiology; D041681:NIH 3T3 Cells; D050722:Oncogene Protein v-cbl / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*
chemical_list: D050722:Oncogene Protein v-cbl