PMID- 11435685
OWN - NLM
STAT- MEDLINE
DCOM- 20010802
LR  - 20220331
IS  - 0301-0171 (Print)
IS  - 0301-0171 (Linking)
VI  - 92
IP  - 3-4
DP  - 2001
TI  - High frequency of spontaneous translocations revealed by FISH in cells from 
      patients with the cancer-prone syndromes ataxia telangiectasia and Nijmegen 
      breakage syndrome.
PG  - 186-91
AB  - The application of fluorescence in situ hybridization (FISH) using 
      whole-chromosome paints (WCPs) is proving to be a very powerful technique for 
      revealing chromosomal instability that, for the most part, has gone undetected by 
      conventional cytogenetic analysis. We have analyzed the frequency of 
      translocations in lymphocytes and lymphoblastoid cell lines from ataxia 
      telangiectasia (AT) and Nijmegen breakage syndrome (NBS) homozygotes and 
      heterozygotes using a three-color chromosome-painting technique (WCP 1, 2, 4). 
      With this assay we were able to detect an increased frequency of spontaneous 
      translocations in AT homozygotes (median, 18.47 +/- 10.82 translocations per 
      1,000 metaphase cells; 10 patients) and AT heterozygotes (median, 7.87 +/- 3.15 
      translocations per 1,000 cells; 7 patients), in comparison to controls (median, 
      2.26 +/- 1.75 translocations per 1,000 cells; 10 controls). Analysis of NBS 
      homozygotes (median, 19.05 +/- 11.27 translocations per 1,000 cells; 5 patients) 
      and NBS heterozygotes (median, 6.93 +/- 3.04 translocations per 1,000 cells; 6 
      patients) also showed an increased frequency of translocations in these patients 
      compared to controls. The presence of such hitherto undetected chromosomal 
      aberrations corroborate previous findings of spontaneous chromosomal instability 
      in AT and NBS patients, as manifested by an increased rate of open breaks and 
      rearrangements involving chromosomes 7 and 14. Moreover, we show that the degree 
      of genomic instability in AT and NBS patients is even higher than previously 
      established and that some AT and NBS heterozygotes evidence spontaneous 
      chromosomal instability as well. These increased levels of nonspecific 
      translocations could be an important risk factor for the development of 
      malignancies in homozygotes and heterozygotes for ATM or NBS1 gene mutations.
CI  - Copyright 2001 S. Karger AG, Basel.
FAU - Stumm, M
AU  - Stumm M
AD  - Institute of Human Genetics, Otto-von-Guericke University, Magdeburg, Germany. 
      Markus.Stumm@medizin.uni-magdeburg.de
FAU - Neubauer, S
AU  - Neubauer S
FAU - Keindorff, S
AU  - Keindorff S
FAU - Wegner, R D
AU  - Wegner RD
FAU - Wieacker, P
AU  - Wieacker P
FAU - Sauer, R
AU  - Sauer R
LA  - eng
PT  - Journal Article
PL  - Switzerland
TA  - Cytogenet Cell Genet
JT  - Cytogenetics and cell genetics
JID - 0367735
SB  - IM
MH  - Ataxia Telangiectasia/*genetics
MH  - Chromosome Breakage/*genetics
MH  - Chromosome Painting
MH  - Chromosomes, Human/genetics
MH  - Gene Frequency/genetics
MH  - Heterozygote
MH  - Homozygote
MH  - Humans
MH  - *In Situ Hybridization, Fluorescence
MH  - Lymphocytes
MH  - Mutagenesis/genetics
MH  - Syndrome
MH  - Translocation, Genetic/*genetics
EDAT- 2001/07/04 10:00
MHDA- 2001/08/03 10:01
CRDT- 2001/07/04 10:00
PHST- 2001/07/04 10:00 [pubmed]
PHST- 2001/08/03 10:01 [medline]
PHST- 2001/07/04 10:00 [entrez]
AID - 56900 [pii]
AID - 10.1159/000056900 [doi]
PST - ppublish
SO  - Cytogenet Cell Genet. 2001;92(3-4):186-91. doi: 10.1159/000056900.