Mutations in Tumor Suppressor Gene NBS1 in Adult Patients with
Seemanová E., 1Hoch J., 2Herzogová J., 3Kawaciuk I., 4Janda J., 5Kohoutová M., 6Seeman P., 7Varon R., 7Sperling K.
Oddělení klinické genetiky Ústavu biologie a lékařské genetiky 2. LF UK, Praha 1Chirurgická klinika 2. LF UK a FNM, Praha 2Dermatologická klinika 2. LF UK a FNM, Praha 3Urologická klinika 2. LF UK a FNM, Praha 4Ústav hematologie a krevní transfuze, Praha 5Ústav biologie 1. LF UK, Praha 6DNA laboratoř Kliniky dětské neurologie 2. LF UK a FNM, Praha 7Institut für Humangenetik, der Humboldt Universität zu Berlin, Německo
Background. Mutations 657del5 and R215W in exon 6 of tumor suppressor gene NBS1 are found in 1% Slavic populations.
Increased occurrence of cancer was repeatedly reported in adult relatives of patients with Nijmegen breakage
syndrome. Among children with oncological problematic, nonsignificantly increased frequency of NBS1 heterozygotes
was found, which seems not to play any important role in cancerogenesis in childhood. However, the
proportion of NBS heterozygotes among adult patients with malignancies could be significant and their therapy and
follow up should respect their hyperradiosensitivity.
Methods and Results. Mutations in exon were studied in 706 adult patients with malignancies. We found 5 NBS
heterozygotes, which not more than the population prevalence (1:129–165). Increased frequency of NBS heterozygotes
was found among patients with colon and rectal cancer (2/101), breast cancer (1/60), skin malignancies (1/98).
Conclusions. Surprisingly only one NBS heterozygote was found among 228 patients with nonHodgkin lymphoma,
the malignancy which is a common complication in NBS homozygotes. Other types of malignancies were uncommon
and only one R215W heterozygote was found. Comparison frequency of NBS heterozygotes with incidence
NBS among person older than 70 years shows significant difference. Prevention of malignancies by avoidance from
ionisation could be realized also in relatives of patients after identification of their genotype.
tumor suppressor gene NBS1, Slavic mutations 657del5 and R215W in exon 6, NBS heterozygotes
among adult patients with malignancies.