Exclusion of the nuclear factor-kappa B3 (REL A) gene as candidate for the multiple endocrine neoplasia type 1 (MEN 1) gene.
Multiple endocrine neoplasia type 1 (MEN 1) is inherited as an autosomal dominant disorder, characterized by neoplasia and hyperplasia in specific endocrine organs. The MEN 1 gene, which is most probably a tumor suppressor gene, has been localized to a region of approximately 900 kb on chromosome 11q13. The nuclear factor-kappa B (NF-kappa B) is a transcription factor with pleiotropic expression, which is involved in the regulation of expression of many cellular genes. The p50/p65 heterodimer is the most abundant form of NF-kappa B. The gene encoding the p65 subunit (NF-kappa B3/REL A) was recently localized in the 900-kb MEN 1 region and was considered a good candidate gene for MEN 1. The structure and nucleotide sequence of the NF-kappa B3 coding region in MEN 1 patients were compared with those of non-MEN 1 subjects, to determine the potential role of this gene in MEN 1 tumorigenesis. Southern blot analysis with constitutional DNA from probands of 14 independent MEN 1 families and DNA from four MEN 1 tumor specimens did not reveal any structural abnormality of the NF-kappa B3 gene. Direct sequencing of cDNAs from two affected subjects from 2 different MEN 1 families, as well as nucleotide sequence analysis of exon/intron boundaries in these patients, did not reveal MEN 1-specific point mutations or other small structural aberrations in the NF-kappa B3 gene. These results make it very unlikely that the NF-kappa B3 gene is the gene responsible for the development of MEN 1.
Landsvater
R M
RM
Department of Internal Medicine, University Hospital Utrecht, The Netherlands.
de Wit
M J
MJ
Peterson
L F
LF
Sinke
R J
RJ
Geurts van Kessel
A
A
Lips
C J
CJ
Höppener
J W
JW
D001483:Base Sequence; D018076:DNA, Complementary; D004273:DNA, Neoplasm / Q000032:analysis*; D006801:Humans; D008969:Molecular Sequence Data; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics*; D016328:NF-kappa B / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D051996:Transcription Factor RelA
D018076:DNA, Complementary; D004273:DNA, Neoplasm; D016328:NF-kappa B; D009687:Nuclear Proteins; D051996:Transcription Factor RelA