PMID- 35052422
OWN - NLM
STAT- MEDLINE
DCOM- 20220222
LR  - 20220222
IS  - 2073-4425 (Electronic)
IS  - 2073-4425 (Linking)
VI  - 13
IP  - 1
DP  - 2021 Dec 28
TI  - BRCA2 Haploinsufficiency in Telomere Maintenance.
LID - 10.3390/genes13010083 [doi]
LID - 83
AB  - 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.
FAU - Gunnarsdottir, Soffia R
AU  - Gunnarsdottir SR
AD  - BioMedical Center, School of Health Sciences, Faculty of Medicine, University of 
      Iceland, 101 Reykjavik, Iceland.
FAU - Bjarnason, Hordur
AU  - Bjarnason H
AD  - BioMedical Center, School of Health Sciences, Faculty of Medicine, University of 
      Iceland, 101 Reykjavik, Iceland.
FAU - Thorvaldsdottir, Birna
AU  - Thorvaldsdottir B
AD  - BioMedical Center, School of Health Sciences, Faculty of Medicine, University of 
      Iceland, 101 Reykjavik, Iceland.
FAU - Paland, Felice
AU  - Paland F
AD  - BioMedical Center, School of Health Sciences, Faculty of Medicine, University of 
      Iceland, 101 Reykjavik, Iceland.
AD  - Faculty of Medicine, Eberhard Karls University, 72074 Tubingen, Germany.
FAU - Steinarsdottir, Margret
AU  - Steinarsdottir M
AD  - Department of Genetics and Molecular Medicine, Landspitali the National 
      University Hospital of Iceland, 101 Reykjavik, Iceland.
FAU - Eyfjord, Jorunn E
AU  - Eyfjord JE
AD  - BioMedical Center, School of Health Sciences, Faculty of Medicine, University of 
      Iceland, 101 Reykjavik, Iceland.
FAU - Bodvarsdottir, Sigridur K
AU  - Bodvarsdottir SK
AUID- ORCID: 0000-0001-8799-8018
AD  - BioMedical Center, School of Health Sciences, Faculty of Medicine, University of 
      Iceland, 101 Reykjavik, Iceland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211228
PL  - Switzerland
TA  - Genes (Basel)
JT  - Genes
JID - 101551097
RN  - 0 (BRCA2 Protein)
RN  - 0 (BRCA2 protein, human)
SB  - IM
MH  - BRCA2 Protein/*genetics
MH  - Breast Neoplasms/genetics/*pathology
MH  - Female
MH  - *Genetic Predisposition to Disease
MH  - *Haploinsufficiency
MH  - *Heterozygote
MH  - Humans
MH  - *Mutation
MH  - *Telomere Shortening
PMC - PMC8775325
OTO - NOTNLM
OT  - BRCA2
OT  - Fanconi anemia
OT  - chromosomal instability
OT  - haploinsufficiency
OT  - telomere
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript, or in the decision to publish the results.
EDAT- 2022/01/22 06:00
MHDA- 2022/02/23 06:00
PMCR- 2021/12/28
CRDT- 2022/01/21 01:02
PHST- 2021/09/17 00:00 [received]
PHST- 2021/12/13 00:00 [revised]
PHST- 2021/12/23 00:00 [accepted]
PHST- 2022/01/21 01:02 [entrez]
PHST- 2022/01/22 06:00 [pubmed]
PHST- 2022/02/23 06:00 [medline]
PHST- 2021/12/28 00:00 [pmc-release]
AID - genes13010083 [pii]
AID - genes-13-00083 [pii]
AID - 10.3390/genes13010083 [doi]
PST - epublish
SO  - Genes (Basel). 2021 Dec 28;13(1):83. doi: 10.3390/genes13010083.