Multiplex single-tube screening for mutations in the Nijmegen Breakage Syndrome (NBS1) gene in Hodgkin's and non-Hodgkin's lymphoma patients of Slavic origin.
Patients with Nijmegen Breakage Syndrome (NBS) have a high risk to develop malignant diseases, most frequently B-cell lymphomas. It has been demonstrated that this chromosomal breakage syndrome results from mutations in the NBS1 gene that cause either a loss of full-length protein expression or expression of a variant protein. A large proportion of the known NBS patients are of Slavic origin who carry a major founder mutation 657del5 in exon 6 of the NBS1 gene. The prevalence of this mutation in Slav populations is reported to be high, possibly contributing to higher cancer risk in these populations. Therefore, if mutations in NBS1 are associated with higher risk of developing lymphoid cancers it would be most likely to be observed in these populations. A multiplex assay for four of the most frequent NBS1 mutations was designed and a series of 119 lymphoma patients from Slavic origin as well as 177 healthy controls were tested. One of the patients was a heterozygote carrier of the ACAAA deletion mutation in exon 6 (1/119). No mutation was observed in the control group, despite the reported high frequency (1/177). The power of this study was 30% to detect a relative risk of 2.0.
1Biotransformations Group, Center of Occupational Diseases, National Institute of Public Health, Prague 10, 100 42, Czech Republic.
Pavel
P
Soucek
Ivan
I
Gut
Marek
M
Trneny
Eva
E
Skovlund
Grethe
G
Grenaker Alnaes
Tom
T
Kristensen
Anne-Lise
AL
Børresen-Dale
Vessela N
VN
Kristensen
D018797:Cell Cycle Proteins / Q000235:genetics*; D043171:Chromosomal Instability / Q000235:genetics*; D005820:Genetic Testing; D006689:Hodgkin Disease / Q000235:genetics*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D044465:White People
D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins