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Germline mutations and polymorphisms in the NFKBIA gene in Hodgkin lymphoma
Author(s) -
Osborne Julie,
Lake Annette,
Alexander Freda E.,
Taylor G. Malcolm,
Jarrett Ruth F.
Publication year - 2005
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21036
Subject(s) - germline , germline mutation , missense mutation , biology , gene , genetics , somatic cell , mutation , lymphoma , cancer research , coding region , microbiology and biotechnology , immunology
Somatic inactivation of NFKBIA , the gene encoding IκBα, is a frequent occurrence in the malignant Hodgkin and Reed‐Sternberg (HRS) cells of Hodgkin lymphoma (HL). Impairment of IκBα function results in deregulated NF‐κB 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. © 2005 Wiley‐Liss, Inc.