Evidence map›Paper›PMID 36991492›Full record

ArticleGenome biology2023

CRISPR screens identify gene targets at breast cancer risk loci.

Natasha K Tuano, Jonathan Beesley, Murray Manning, Wei Shi, Laura Perlaza-Jimenez, Luis F Malaver-Ortega, Jacob M Paynter, Debra Black, Andrew Civitarese, Karen McCue and 12 more

Open access · goldAbstract read
In one paragraph

Article in Genome biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
4.8field-weighted citation impact, top 5% 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

20 citing papers in PubMed, 31 citations in OpenAlex.

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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

22 authors at 6 institutions in 2 countries.

Natasha K TuanoCancer Research Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.
Jonathan BeesleyCancer Program, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Murray ManningCancer Research Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.
Wei ShiCancer Program, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Laura Perlaza-JimenezCancer Research Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.
Luis F Malaver-OrtegaFunctional Genomics Platform, Monash University, Clayton, VIC, Australia.
Jacob M PaynterCancer Research Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.
Debra BlackCancer Program, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Andrew CivitareseCancer Program, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Karen McCueCancer Program, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Aaron HatzipantelisCancer Program, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Kristine HillmanCancer Program, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Susanne KaufmannCancer Program, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Haran SivakumaranCancer Program, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Jose M PoloDevelopment and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, VIC, Australia.
Roger R ReddelCancer Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia.
Vimla BandDepartment of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, USA.
Juliet D FrenchCancer Program, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Stacey L EdwardsCancer Program, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
David R PowellBioinformatics Platform, Monash University, Clayton, VIC, Australia.
Georgia Chenevix-TrenchCancer Program, QIMR Berghofer Medical Research Institute, Brisbane, Australia. Georgia.Trench@qimrberghofer.edu.au.
Joseph RosenbluhCancer Research Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia. sefi.rosenbluh@monash.edu.ORCID 0000-0001-9815-8049
QIMR Berghofer Medical Research Institute · AUAustralian Regenerative Medicine Institute · AUMonash University · AUDiscovery Institute · USThe University of Sydney · AUUniversity of Nebraska Medical Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGenome-wide association studies (GWAS) have identified > 200 loci associated with breast cancer risk. The majority of candidate causal variants are in non-coding regions and likely modulate cancer risk by regulating gene expression. However, pinpointing the exact target of the association, and identifying the phenotype it mediates, is a major challenge in the interpretation and translation of GWAS.

resultsHere, we show that pooled CRISPR screens are highly effective at identifying GWAS target genes and defining the cancer phenotypes they mediate. Following CRISPR mediated gene activation or suppression, we measure proliferation in 2D, 3D, and in immune-deficient mice, as well as the effect on DNA repair. We perform 60 CRISPR screens and identify 20 genes predicted with high confidence to be GWAS targets that promote cancer by driving proliferation or modulating the DNA damage response in breast cells. We validate the regulation of a subset of these genes by breast cancer risk variants.

conclusionsWe demonstrate that phenotypic CRISPR screens can accurately pinpoint the gene target of a risk locus. In addition to defining gene targets of risk loci associated with increased breast cancer risk, we provide a platform for identifying gene targets and phenotypes mediated by risk variants.

Indexed as

Genome-Wide Association StudyNeoplasmsAnimalsClustered Regularly Interspaced Short Palindromic RepeatsGenetic Predisposition to DiseaseMicePhenotypePolymorphism, Single NucleotideBreast cancer riskFunctional phenotypic screensPost GWASTarget discovery

Identifiers

PMID36991492
PMCPMC10053147
OpenAlexW4361199386

What OpenQuestion holds

Textmetadata
LicenceCC BY
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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.