Evidence map›Paper›PMID 39010058›Full record

ArticleBMC medical genomics2024

Co-expression in tissue-specific gene networks links genes in cancer-susceptibility loci to known somatic driver genes.

Carlos G Urzúa-Traslaviña, Tijs van Lieshout, Floranne Boulogne, Kevin Domanegg, Mahmoud Zidan, Olivier B Bakker, Annique Claringbould, Jeroen de Ridder, Wilbert Zwart, Harm-Jan Westra and 2 more

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Article in BMC medical genomics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–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

2 citing papers in PubMed.

  1. Article
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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

12 authors.

Carlos G Urzúa-Traslaviña *Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands.
Tijs van Lieshout *Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands.
Floranne Boulogne *Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands.
Kevin DomaneggDepartment of Genetics, University Medical Center Groningen, Groningen, The Netherlands.
Mahmoud ZidanDepartment of Genetics, University Medical Center Groningen, Groningen, The Netherlands.
Olivier B BakkerWellcome Sanger Institute, Human Genetics, Hinxton, UK.
Annique ClaringbouldDepartment of Genetics, University Medical Center Groningen, Groningen, The Netherlands.
Jeroen de RidderOncode Institute, Utrecht, The Netherlands.
Wilbert ZwartOncode Institute, Utrecht, The Netherlands.
Harm-Jan WestraDepartment of Genetics, University Medical Center Groningen, Groningen, The Netherlands.
Patrick DeelenDepartment of Genetics, University Medical Center Groningen, Groningen, The Netherlands.
Lude FrankeDepartment of Genetics, University Medical Center Groningen, Groningen, The Netherlands. l.h.franke@umcg.com.

Funding

Epidemiologic StudiesU19CA148065 · NCI · HARVARD SCHOOL OF PUBLIC HEALTH · PI AHSAN, HABIBUL, BRUGGE, JOAN SIEFERT · 2010 to 2014
$10.6M
Epidemiological and Clinical Translational Studies Post Genome-Wide AssociationU19CA148537 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI EASTON, DOUGLAS FREDERICK, EELES, ROSALIND · 2010 to 2014
$10.4M
Ovarian cancer GWAS discovery, expansion and replication (N2 - Project #1)U19CA148112 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI SELLERS, THOMAS A · 2010 to 2014
$10.2M
A genome-wide association study for breast cancer in BRCA1 mutation carriersR01CA128978 · NCI · MAYO CLINIC ROCHESTER · PI COUCH, FERGUS JOSEPH · 2008 to 2012
$4.8M
Cancer Research UKCIHREuropean Research Council 637640NCI NIH HHS R01 CA128978NCI NIH HHS U19 CA148065NCI NIH HHS U19 CA148112NCI NIH HHS U19 CA148537NCI NIH HHS X01 HG007492Nederlandse Organisatie voor Wetenschappelijk Onderzoek 9150161910057Oncode Institute Senior Investigator Lude FrankeSaxum Volutum Pericode
6 · The paper itself

Abstract

backgroundThe genetic background of cancer remains complex and challenging to integrate. Many somatic mutations within genes are known to cause and drive cancer, while genome-wide association studies (GWAS) of cancer have revealed many germline risk factors associated with cancer. However, the overlap between known somatic driver genes and positional candidate genes from GWAS loci is surprisingly small. We hypothesised that genes from multiple independent cancer GWAS loci should show tissue-specific co-regulation patterns that converge on cancer-specific driver genes.

resultsWe studied recent well-powered GWAS of breast, prostate, colorectal and skin cancer by estimating co-expression between genes and subsequently prioritising genes that show significant co-expression with genes mapping within susceptibility loci from cancer GWAS. We observed that the prioritised genes were strongly enriched for cancer drivers defined by COSMIC, IntOGen and Dietlein et al. The enrichment of known cancer driver genes was most significant when using co-expression networks derived from non-cancer samples of the relevant tissue of origin.

conclusionWe show how genes within risk loci identified by cancer GWAS can be linked to known cancer driver genes through tissue-specific co-expression networks. This provides an important explanation for why seemingly unrelated sets of genes that harbour either germline risk factors or somatic mutations can eventually cause the same type of disease.

Indexed as

Gene Regulatory NetworksGenetic Predisposition to DiseaseGenome-Wide Association StudyNeoplasmsGene Expression Regulation, NeoplasticGenetic LociHumansOrgan SpecificityBreast cancerCancer driversCancer susceptibility genesColon cancerGene networksGWASOmnigenicProstate cancerrecount3Tissue-specific

Identifiers

PMID39010058
PMCPMC11247850

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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.