title: Incidence and prognostic relevance of genetic variations in T-cell lymphoblastic lymphoma in childhood and adolescence.
abstract: Probability of event-free survival (pEFS) in pediatric T-cell lymphoblastic lymphoma is about 80%, whereas survival in relapsed patients is very poor. No stratification criteria have been established so far. Recently, activating NOTCH1 mutations were reported to be associated with favorable prognosis, and loss of heterozygosity at chromosome 6q (LOH6q) was reported to be associated with increased relapse risk. The current project was intended to evaluate the prognostic effect of these markers. Mutations in hot spots of NOTCH1 and FBXW7 were analyzed in 116 patients. Concerning LOH6q status, 118 patients were investigated, using microsatellite marker analysis, in addition to an earlier reported cohort of 99 available patients. Ninety-two cases were evaluable for both analyses. All patients were treated with T-cell lymphoblastic lymphoma-Berlin-Frankfurt-Münster group (BFM)-type treatment. LOH6q was observed in 12% of patients (25/217) and associated with unfavorable prognosis (pEFS 27% ± 9% vs 86% ± 3%; P < .0001). In 60% (70/116) of the patients, NOTCH1 mutations were detected and associated with favorable prognosis (pEFS 84% ± 5% vs 66% ± 7%; P = .021). Interestingly, NOTCH1 mutations were rarely observed in patients with LOH in 6q16. Both prognostic markers will be used as stratification criteria in coming Non-Hodgkin Lymphoma-BFM trials.
authors: Non-Hodgkin Lymphoma Berlin-Frankfurt-Münster Group Study Center and Department of Pediatric Hematology and Oncology, Justus Liebig University, Giessen, Germany.
authors: Bettina R
authors: BR
authors: Bonn
authors: Marius
authors: M
authors: Rohde
authors: Martin
authors: M
authors: Zimmermann
authors: David
authors: D
authors: Krieger
authors: Ilske
authors: I
authors: Oschlies
authors: Felix
authors: F
authors: Niggli
authors: Grazyna
authors: G
authors: Wrobel
authors: Andishe
authors: A
authors: Attarbaschi
authors: Gabriele
authors: G
authors: Escherich
authors: Wolfram
authors: W
authors: Klapper
authors: Alfred
authors: A
authors: Reiter
authors: Birgit
authors: B
authors: Burkhardt
mesh_terms: D000293:Adolescent; D018797:Cell Cycle Proteins / Q000235:genetics; D002648:Child; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D044783:F-Box Proteins / Q000235:genetics; D000073979:F-Box-WD Repeat-Containing Protein 7; D005260:Female; D014644:Genetic Variation; D006801:Humans; D015994:Incidence; D019656:Loss of Heterozygosity; D016399:Lymphoma, T-Cell / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D009154:Mutation; D011379:Prognosis; D051881:Receptor, Notch1 / Q000235:genetics*; 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