title: Mutations and molecular variants of the NBS1 gene in non-Hodgkin lymphoma.
abstract: Non-Hodgkin lymphomas (NHLs) are characterized by chromosomal translocations that juxtapose loci encoding lymphoid antigen receptors with cellular proto-oncogenes. These translocations are thought to arise from inaccurate processing of DNA breaks created during physiologic recombination of the antigen receptor genes in lymphocytes. The inherited disorders ataxia-telangiectasia and Nijmegen breakage syndrome are caused by mutations in the ATM and NBS1 genes, respectively, and are characterized by generalized genomic instability and a high incidence of lymphoid cancers. Lymphoid cells from patients with either disorder frequently have chromosomal translocations involving T-cell-receptor or immunoglobulin loci. To investigate the potential role of the NBS1 gene in the pathogenesis of NHL, we screened tumor DNA samples from 91 sporadic cases of NHL and genomic DNA from 154 control individuals for mutations in all 16 exons of the NBS1 gene and in flanking intronic sequences. One NHL case with a truncating mutation in NBS1 and a second NHL case with a putative missense mutation were detected. Neither mutation was observed among controls. Three additional putative missense mutations were observed only in the normal control samples. A panel of six common polymorphisms spanning the NBS1 gene was genotyped and provided no evidence for loss of heterozygosity in the NHL cases with mutations or in the NHL population overall. These results suggest that mutations in NBS1 do not play a major role in the development of NHL in the United States.
mesh_terms: D000483:Alleles; D018797:Cell Cycle Proteins / Q000235:genetics*; D005091:Exons / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008228:Lymphoma, Non-Hodgkin / Q000209:etiology / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins