BRCA2 Haploinsufficiency in Telomere Maintenance

Genes (Basel). 2021 Dec 28;13(1):83. doi: 10.3390/genes13010083.


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.

Keywords: BRCA2; Fanconi anemia; chromosomal instability; haploinsufficiency; telomere.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • BRCA2 Protein / genetics*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Female
  • Genetic Predisposition to Disease*
  • Haploinsufficiency*
  • Heterozygote*
  • Humans
  • Mutation*
  • Telomere Shortening*


  • BRCA2 Protein
  • BRCA2 protein, human