Mutations in the Nijmegen Breakage Syndrome gene (NBS1) in childhood acutelymphoblastic leukemia (ALL)

Citation
R. Varon et al., Mutations in the Nijmegen Breakage Syndrome gene (NBS1) in childhood acutelymphoblastic leukemia (ALL), CANCER RES, 61(9), 2001, pp. 3570-3572
Citations number
21
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
CANCER RESEARCH
ISSN journal
0008-5472 → ACNP
Volume
61
Issue
9
Year of publication
2001
Pages
3570 - 3572
Database
ISI
SICI code
0008-5472(20010501)61:9<3570:MITNBS>2.0.ZU;2-5
Abstract
The Nijmegen Breakage Syndrome (NBS) is a rare autosomal recessive disorder associated with immune deficiency, chromosome fragility, and increased sus ceptibility to lymphoid malignancies. The aim of the present study was to e lucidate the potential role of the gene mutated in NBS (NBS1) in the pathog enesis and disease progression of childhood acute lymphoblastic leukemia (A LL), Samples from 47 children with first relapse of ALL were analyzed for m utations in all 16 exons of the NBS1 gene, and in 7 of them (14.9%), four n ovel amino acid substitutions were identified. Mutations S93L, D95N, and I1 71V occur in the two known domains of nibrin that are probably involved in protein-protein interactions. Germ-line origin of the I171V mutation was co nfirmed in three patients, whereas the D95N exchange was present only in le ukemic cells. The R215W mutation was observed in one ALL but also in a popu lation-based study and probably represents a rare sequence variant. No addi tional mutations were found on the second allele in any of these seven pati ents, The observed NBS1 gene mutations in ALL patients points to its possib le involvement in the pathogenesis of this disease.