title: FBXW7 and NOTCH1 mutations in childhood T cell acute lymphoblastic leukaemia and T cell non-Hodgkin lymphoma.
abstract: Mutation analysis of FBXW7 and NOTCH1 genes was performed in 55 T cell acute lymphoblastic leukaemia (T-ALL) and 14 T cell non-Hodgkin lymphoma (T-NHL) patients who were treated on the Japan Association of Childhood Leukaemia Study (JACLS) protocols ALL-97 and NHL-98. FBXW7 and/or NOTCH1 mutations were found in 22 (40.0%) of 55 T-ALL and 7 (50.0%) of 14 T-NHL patients. FBXW7 mutations were found in 8 (14.6%) of 55 T-ALL and 3 (21.4%) of 14 T-NHL patients, and NOTCH1 mutations in 17 (30.9%) of 55 T-ALL and 6 (42.9%) of 14 T-NHL patients. Three (5.4%) T-ALL and two (1.4%) T-NHL patients had mutations in both FBXW7 and NOTCH1. FBXW7 mutations included one insertion, one deletion, one deletion/insertion and nine missense mutations. NOTCH1 mutations were detected in the heterodimerization domain (HD) in 15 cases, in the PEST domain in seven cases, and in both the HD and PEST domains in one case. Five-year event-free survival and overall survival for patients with FBXW7 and/or NOTCH1 mutations were 95.5% (95% CI, 71.9-99.4%) and 100% respectively, suggesting that T-ALL patients with FBXW7 and/or NOTCH1 mutation represent a good prognosis compared to those without FBXW7 and/or NOTCH1 mutations (63.6%, P = 0.007 and 78.8%, P = 0.023, respectively).
authors.affiliation: Department of Haematology/Oncology, Gunma Children's Medical Centre, Gunma, Japan.
authors.forename: Myoung-Ja
authors.initials: MJ
authors.lastname: Park
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Taki
authors.forename: Megumi
authors.initials: M
authors.lastname: Oda
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Watanabe
authors.forename: Keiko
authors.initials: K
authors.lastname: Yumura-Yagi
authors.forename: Ryoji
authors.initials: R
authors.lastname: Kobayashi
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Suzuki
authors.forename: Junichi
authors.initials: J
authors.lastname: Hara
authors.forename: Keizo
authors.initials: K
authors.lastname: Horibe
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Hayashi
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics*; D016009:Chi-Square Distribution; D002648:Child; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D044783:F-Box Proteins / Q000235:genetics*; D000073979:F-Box-WD Repeat-Containing Protein 7; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D053208:Kaplan-Meier Estimate; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000401:mortality; D008297:Male; D009154:Mutation; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000401:mortality; D051881:Receptor, Notch1 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; D051881:Receptor, Notch1; D044767:Ubiquitin-Protein Ligases