Evidence map›Paper›PMID 39528827›Full record

ArticleNature genetics2024

Brca1 haploinsufficiency promotes early tumor onset and epigenetic alterations in a mouse model of hereditary breast cancer.

Carman Man-Chung Li, Alyssa Cordes, Michael U J Oliphant, S Aidan Quinn, Mayura Thomas, Laura M Selfors, Francesca Silvestri, Nomeda Girnius, Gianmarco Rinaldi, Jason J Zoeller and 8 more

Erratum issuedAbstract read
PubMed Publisher
In one paragraph

Article in Nature genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

11 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Guideline
  2. Review
  3. JAK2Leukemia · 2026
    Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Carman Man-Chung LiDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA. carman_li@hms.harvard.edu.ORCID http://orcid.org/0000-0002-0577-7797
Alyssa CordesDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0009-0008-0644-8136
Michael U J OliphantDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.
S Aidan QuinnDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Mayura ThomasDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.
Laura M SelforsDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.
Francesca SilvestriDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-2540-8267
Nomeda GirniusDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-7267-5950
Gianmarco RinaldiDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.
Jason J ZoellerDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.
Hana ShapiroDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.
Christina TsiobikasDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.
Kushali P GuptaDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.
Shailja PathaniaDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Aviv RegevKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-3293-3158
Cigall KadochDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-4058-5985
Senthil K MuthuswamyCancer Research Institute, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Joan S BruggeDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA. joan_brugge@hms.harvard.edu.ORCID http://orcid.org/0000-0002-2547-4814

Funding

Tracking the evolution of breast cancer through single cell analyses of premalignant breast tissues from women at high risk for cancer developmentR35CA242428 · NCI · HARVARD MEDICAL SCHOOL · PI BRUGGE, JOAN SIEFERT · 2019 to 2025
$7.1M
A Novel BRCA1 Heterozygosity Driven Breast Cancer Mouse Model to Identify Tumor Initiating Events and Therapeutic StrategiesR03CA270831 · NCI · UNIVERSITY OF MASSACHUSETTS BOSTON · PI PATHANIA, SHAILJA · 2022 to 2023
$153k
NCI NIH HHS R03 CA270831NCI NIH HHS R35 CA242428
6 · The paper itself

Abstract

Germline BRCA1 mutation carriers face a high breast cancer risk; however, the underlying mechanisms for this risk are not completely understood. Using a new genetically engineered mouse model of germline Brca1 heterozygosity, we demonstrate that early tumor onset in a Brca1 heterozygous background cannot be fully explained by the conventional 'two-hit' hypothesis, suggesting the existence of inherent tumor-promoting alterations in the Brca1 heterozygous state. Single-cell RNA sequencing and assay for transposase-accessible chromatin with sequencing analyses uncover a unique set of differentially accessible chromatin regions in ostensibly normal Brca1 heterozygous mammary epithelial cells, distinct from wild-type cells and partially mimicking the chromatin and RNA-level changes in tumor cells. Transcription factor analyses identify loss of ELF5 and gain of AP-1 sites in these epigenetically primed regions; in vivo experiments further implicate AP-1 and Wnt10a as strong promoters of Brca1-related breast cancer. These findings reveal a previously unappreciated epigenetic effect of Brca1 haploinsufficiency in accelerating tumorigenesis, advancing our mechanistic understanding and informing potential therapeutic strategies.

Indexed as

BRCA1 ProteinDisease Models, AnimalEpigenesis, GeneticHaploinsufficiencyAnimalsBreast NeoplasmsChromatinFemaleGene Expression Regulation, NeoplasticGerm-Line MutationHumansMiceBRCA1 ProteinBrca1 protein, mouseChromatin

Identifiers

PMID39528827

What OpenQuestion holds

Textmetadata
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.