Evidence map›Paper›PMID 31251913›Full record

ArticleCell2019

Inadequate DNA Damage Repair Promotes Mammary Transdifferentiation, Leading to BRCA1 Breast Cancer.

Hua Wang, Dongxi Xiang, Ben Liu, Aina He, Helena J Randle, Kelvin Xi Zhang, Anushka Dongre, Norman Sachs, Allison P Clark, Luwei Tao and 7 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
5.2field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

65 citing papers in PubMed, 102 citations in OpenAlex.

  1. Genome stability disrupted by the circRBM39(4,5,6)-RPA2 axis represses breast tumorigenesis.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  2. Review
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  4. RUNX1-deficiency drives immune-active ERbioRxiv : the preprint server for biology · 2026
    Article
  5. Article
  6. Article
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  8. Article
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  10. Review
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  15. Review
  16. Review
  17. Article
  18. Cells-of-Origin of Breast Cancer and Intertumoral Heterogeneity.Advances in experimental medicine and biology · 2025
    Review
  19. Article
  20. The mFrontiers in oncology · 2025
    Article

5 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 7 institutions in 2 countries.

Hua WangDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Departments of Genetics and Medicine, Harvard Medical School, Boston, MA 02115, USA.
Dongxi XiangDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Ben LiuDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Departments of Genetics and Medicine, Harvard Medical School, Boston, MA 02115, USA.
Aina HeDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Helena J RandleDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Departments of Genetics and Medicine, Harvard Medical School, Boston, MA 02115, USA.
Kelvin Xi ZhangInformatics IT, Merck & Co., Boston, MA 02115, USA.
Anushka DongreWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Norman SachsHubrecht Institute, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
Allison P ClarkDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Departments of Genetics and Medicine, Harvard Medical School, Boston, MA 02115, USA.
Luwei TaoDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Qing ChenDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Vladimir V BotchkarevDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Departments of Genetics and Medicine, Harvard Medical School, Boston, MA 02115, USA.
Ying XieDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Ning DaiDepartment of Medicine, Robert Wood Johnson Medical School, Rutgers, New Brunswick, NJ 08901, USA.
Hans CleversHubrecht Institute, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
Zhe LiDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address: zli4@rics.bwh.harvard.edu.
David M LivingstonDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Departments of Genetics and Medicine, Harvard Medical School, Boston, MA 02115, USA. Electronic address: david_livingston@dfci.harvard.edu.
Harvard University · USBrigham and Women's Hospital · USDana-Farber Cancer Institute · USHubrecht Institute for Developmental Biology and Stem Cell Research · NLJohnson University · USMerck & Co., Inc., Rahway, NJ, USA (United States) · USWhitehead Institute for Biomedical Research · US

Funding

Use of Organotypic and Mammary Gland Models to Investigate the Outcomes of ClonalP01CA080111 · NCI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI DILLON, DEBORAH · 1999 to 2018
$36.0M
BRCA1 Function in Post-Damage Nuclear FociR01CA136512 · NCI · DANA-FARBER CANCER INST · PI LIVINGSTON, DAVID MORSE · 2009 to 2019
$4.6M
Deciphering the mechanism underlying BRCA1 breast cancer developmentR35CA242143 · NCI · DANA-FARBER CANCER INST · PI LIVINGSTON, DAVID MORSE · 2019 to 2021
$3.0M
Interplay of mammary luminal cells and environmental factors in establishing p53-deficient premalignant fieldR01CA222560 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI LI, ZHE · 2018 to 2022
$1.9M
CRISPR/Cas9-based lineage tracing for fate mapping of cancer cells and stem cellsR21CA205825 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI LI, ZHE · 2016 to 2017
$420k
NCI NIH HHS P01 CA080111NCI NIH HHS R01 CA136512NCI NIH HHS R01 CA222560NCI NIH HHS R21 CA205825NCI NIH HHS R35 CA242143
6 · The paper itself

Abstract

Loss of BRCA1 p220 function often results in basal-like breast cancer (BLBC), but the underlying disease mechanism is largely opaque. In mammary epithelial cells (MECs), BRCA1 interacts with multiple proteins, including NUMB and HES1, to form complexes that participate in interstrand crosslink (ICL) DNA repair and MEC differentiation control. Unrepaired ICL damage results in aberrant transdifferentiation to a mesenchymal state of cultured, human basal-like MECs and to a basal/mesenchymal state in primary mouse luminal MECs. Loss of BRCA1, NUMB, or HES1 or chemically induced ICL damage in primary murine luminal MECs results in persistent DNA damage that triggers luminal to basal/mesenchymal transdifferentiation. In vivo single-cell analysis revealed a time-dependent evolution from normal luminal MECs to luminal progenitor-like tumor cells with basal/mesenchymal transdifferentiation during murine BRCA1 BLBC development. Growing DNA damage accompanied this malignant transformation.

Indexed as

AnimalsBRCA1 ProteinBreast NeoplasmsCell DifferentiationCell TransdifferentiationCell Transformation, NeoplasticDisease Models, AnimalDNA DamageDNA RepairEpithelial CellsFemaleHEK293 CellsHumansMammary Glands, AnimalMCF-7 CellsMembrane ProteinsBRCA1 ProteinBRCA1 protein, humanBrca1 protein, mouseHES1 protein, humanMembrane ProteinsNerve Tissue ProteinsNUMB protein, humanTranscription Factor HES-1BRCA1breast cancercell fatecisplatinCtIPEMTHES1ICL repairmouse modelNUMBsingle-cell analysistransdifferentiation

Identifiers

PMID31251913
PMCPMC6716369
OpenAlexW2955360908

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.