scholarly journals BRCA2 Haploinsufficiency in Telomere Maintenance

Genes ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 83
Author(s):  
Soffía R. Gunnarsdottir ◽  
Hördur Bjarnason ◽  
Birna Thorvaldsdottir ◽  
Felice Paland ◽  
Margrét Steinarsdottir ◽  
...  

Our previous studies showed an association between monoallelic BRCA2 germline mutations and dysfunctional telomeres in epithelial mammary cell lines and increased risk of breast cancer diagnosis for women with BRCA2 999del5 germline mutation and short telomeres in blood cells. In the current study, we analyzed telomere dysfunction in lymphoid cell lines from five BRCA2 999del5 mutation carriers and three Fanconi Anemia D1 patients by fluorescence in situ hybridization (FISH). Metaphase chromosomes were harvested from ten lymphoid cell lines of different BRCA2 genotype origin and analyzed for telomere loss (TL), multitelomeric signals (MTS), interstitial telomere signals (ITS) and extra chromosomal telomere signals (ECTS). TL, ITS and ECTS were separately found to be significantly increased gradually between the BRCA2+/+, BRCA2+/- and BRCA2-/- lymphoid cell lines. MTS were found to be significantly increased between the BRCA2+/+ and the BRCA2+/- heterozygous (p < 0.0001) and the BRCA2-/- lymphoid cell lines (p < 0.0001) but not between the BRCA2 mutated genotypes. Dysfunctional telomeres were found to be significantly increased in a stepwise manner between the BRCA2 genotypes indicating an effect of BRCA2 haploinsufficiency on telomere maintenance.

Toxicology ◽  
2005 ◽  
Vol 210 (1) ◽  
pp. 81-91 ◽  
Author(s):  
Fiorenza Minervini ◽  
Francesca Fornelli ◽  
Giacomo Lucivero ◽  
Ciro Romano ◽  
Angelo Visconti

1981 ◽  
Vol 23 (1) ◽  
pp. 35-38 ◽  
Author(s):  
Ichiro Matsuda ◽  
Izumi Akaboshi ◽  
Jiro Yamamoto ◽  
Noriyuki Nagata

1986 ◽  
Vol 6 (2) ◽  
pp. 703-706
Author(s):  
F Toneguzzo ◽  
A C Hayday ◽  
A Keating

The technique of DNA transfer by electroporation was investigated in an effort to evaluate its utility for the identification of developmentally controlled regulatory sequences. Transient and stable gene expression was detected in a variety of lymphoid cell lines subjected to electroporation. No correlation existed between the levels of chloramphenicol acetyltransferase (acetyl-CoA; chloramphenicol 3-O-acetyltransferase, EC 2.3.1.28) expression and stable transfection frequency. In all lymphoid cell lines tested, the simian virus 40 early region was a better promoter than was the Rous sarcoma virus long terminal repeat.


1977 ◽  
Vol 146 (6) ◽  
pp. 1809-1814 ◽  
Author(s):  
R A Vande Stouwe ◽  
H G Kunkel ◽  
J P Halper ◽  
M E Weksler

Autologous mixed lymphocyte culture (MLC) reactions were studied utilizing autologous purified B cells and autologous established B lymphoid cell lines as stimulating cells. Similar results were obtained although somewhat greater stimulation of lymphocyte proliferation was found with the autologous lymphoid cell lines. Cytotoxic T cells were not generated against the stimulating cells in either case when peripheral blood cells were used as targets. A low cytotoxicity was detected when lymphoid cell lines were used both as stimulators and target cells. However this was nonspecific and was always greater for heterologous lines than for the stimulator line. Third-party cell experiments demonstrated that the autologous reaction could serve as a proliferative stimulus for specific cytotoxic lymphocyte generation. Heat-treated allogeneic lymphocytes that alone do not stimulate proliferation ro cytotoxic T-cell generation in MLC reactions when added to the autologous system produced specific cytotoxic cells. The separation of the proliferative phase from the cytotoxic cell generation was especially striking in these experiments. Possible uses of this system for the generation of specific cytotoxic cells to other nonstimulatory cells are discussed.


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