ArticleNature communications2015
Haploinsufficiency for BRCA1 leads to cell-type-specific genomic instability and premature senescence.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
What it found
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Who cites it
91 citing papers in PubMed, 138 citations in OpenAlex.
- Pathogenic germline variants in BRCA1/2 are associated with a decreased number of hypomethylated rDNA copies.Breast cancer research : BCR · 2026Article
- Why are Some Tissues More Vulnerable? Revisiting Tissue Specificity in Hereditary Cancer Syndromes.Molecular diagnosis & therapy · 2026Review
- Insights from three decades of BRCA1/2 modeling in mice.Nature genetics · 2026Review
- Natural menopause, menarche and breast cancer risk in BRCA1 and BRCA2 pathogenic variant carriers: a Mendelian randomization analysis.British journal of cancer · 2026Article
- Mutational profiles of spontaneous and radiation-related mammary carcinomas in a rat model of Brca1 haploinsufficiency.Scientific reports · 2026Article
- Article
- Homologous recombination pathway alterations in basal-like breast cancer.Frontiers in oncology · 2026Review
- Molecular reflex testing in patients with early metastatic castration-resistant prostate cancer within the PROMPT-study.British journal of cancer · 2026Observational
- Genomic Perspective on Heterogeneity of Organs and Body Aging.Aging cell · 2026Review
- The CDK12-BRCA1 signaling axis mediates dinaciclib-associated radiosensitivity through p53-mediated cellular senescence.Molecular oncology · 2025Article
- Thirty Years of BRCA1: Mechanistic Insights and Their Impact on Mutation Carriers.Cancer discovery · 2025Review
- The cardio-oncologic burden of breast cancer: molecular mechanisms and importance of preclinical models.Basic research in cardiology · 2025Review
- BRCA1 and BRCA2: from cancer susceptibility to synthetic lethality.Genes & development · 2025Review
- Cells-of-Origin of Breast Cancer and Intertumoral Heterogeneity.Advances in experimental medicine and biology · 2025Review
- Luminal breast epithelial cells of BRCA1 or BRCA2 mutation carriers and noncarriers harbor common breast cancer copy number alterations.Nature genetics · 2024Article
- Brca1 haploinsufficiency promotes early tumor onset and epigenetic alterations in a mouse model of hereditary breast cancer.Nature genetics · 2024Article
- Transcriptome Profiling of Mouse Embryonic Fibroblast Spontaneous Immortalization: A Comparative Analysis.International journal of molecular sciences · 2024Article
- Exploring the effect of BRCA1/2 status on chemotherapy-induced hematologic toxicity in patients with ovarian cancer.Cancer chemotherapy and pharmacology · 2024Article
- A Molecular Characterization of the Allelic Expression of theInternational journal of molecular sciences · 2024Article
- Fusobacterium nucleatum triggers senescence phenotype in gingival epithelial cells.Molecular oral microbiology · 2024Article
31 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 8 institutions in 2 countries.
Funding
Abstract
Although BRCA1 function is essential for maintaining genomic integrity in all cell types, it is unclear why increased risk of cancer in individuals harbouring deleterious mutations in BRCA1 is restricted to only a select few tissues. Here we show that human mammary epithelial cells (HMECs) from BRCA1-mutation carriers (BRCA1(mut/+)) exhibit increased genomic instability and rapid telomere erosion in the absence of tumour-suppressor loss. Furthermore, we uncover a novel form of haploinsufficiency-induced senescence (HIS) specific to epithelial cells, which is triggered by pRb pathway activation rather than p53 induction. HIS and telomere erosion in HMECs correlate with misregulation of SIRT1 leading to increased levels of acetylated pRb as well as acetylated H4K16 both globally and at telomeric regions. These results identify a novel form of cellular senescence and provide a potential molecular basis for the rapid cell- and tissue- specific predisposition of breast cancer development associated with BRCA1 haploinsufficiency.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.