title: Germline mutations and polymorphisms in the NFKBIA gene in Hodgkin lymphoma.
abstract: Somatic inactivation of NFKBIA, the gene encoding IkappaBalpha, is a frequent occurrence in the malignant Hodgkin and Reed-Sternberg (HRS) cells of Hodgkin lymphoma (HL). Impairment of IkappaBalpha function results in deregulated NF-kappaB activity, a characteristic of HRS cells. The molecular basis for familial HL, which accounts for approximately 4% of all HL cases, is unclear. To date, familial HL cases have not been evaluated for germline NFKBIA mutations. We screened the entire NFKBIA gene in 8 individuals with familial HL but found no mutations in the coding region or promoter sequences. We identified the first germline NFKBIA missense mutation in a patient with presumed sporadic HL. The frequency of 4 polymorphisms within the NFKBIA gene and promoter region was investigated in a series of HL and control samples; no significant differences emerged but a novel polymorphism was identified in the promoter region. Overall, our results suggest that germline mutations of NFKBIA are not a significant cause of familial aggregation of HL but may contribute to inherited susceptibility to HL.
authors.affiliation: LRF Virus Centre, Institute of Comparative Medicine, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Julie
authors.initials: J
authors.lastname: Osborne
authors.forename: Annette
authors.initials: A
authors.lastname: Lake
authors.forename: Freda E
authors.initials: FE
authors.lastname: Alexander
authors.forename: G Malcolm
authors.initials: GM
authors.lastname: Taylor
authors.forename: Ruth F
authors.initials: RF
authors.lastname: Jarrett
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D004252:DNA Mutational Analysis; D005260:Female; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006689:Hodgkin Disease / Q000235:genetics*; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
chemical_list: D020672:I-kappa B Proteins