Evidence map›Paper›PMID 34795391›Full record

ArticleCommunications biology2021

Precancerous liver diseases do not cause increased mutagenesis in liver stem cells.

Luan Nguyen, Myrthe Jager, Ruby Lieshout, Petra E de Ruiter, Mauro D Locati, Nicolle Besselink, Bastiaan van der Roest, Roel Janssen, Sander Boymans, Jeroen de Jonge and 7 more

Open access · goldAbstract read
In one paragraph

Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.3field-weighted citation impact, top 22% 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

10 citing papers in PubMed, 22 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

17 authors at 4 institutions in 1 country.

Luan Nguyen *Center for Molecular Medicine and Oncode Institute, University Medical Center Utrecht, Utrecht, The Netherlands.ORCID 0000-0003-2788-6625
Myrthe Jager *Center for Molecular Medicine and Oncode Institute, University Medical Center Utrecht, Utrecht, The Netherlands.ORCID 0000-0002-1406-1715
Ruby LieshoutErasmus Medical Center, Rotterdam, The Netherlands.ORCID 0000-0002-7848-3933
Petra E de RuiterErasmus Medical Center, Rotterdam, The Netherlands.
Mauro D LocatiCenter for Molecular Medicine and Oncode Institute, University Medical Center Utrecht, Utrecht, The Netherlands.
Nicolle BesselinkCenter for Molecular Medicine and Oncode Institute, University Medical Center Utrecht, Utrecht, The Netherlands.ORCID 0000-0002-8961-4441
Bastiaan van der RoestCenter for Molecular Medicine and Oncode Institute, University Medical Center Utrecht, Utrecht, The Netherlands.ORCID 0000-0002-8985-8964
Roel JanssenCenter for Molecular Medicine and Oncode Institute, University Medical Center Utrecht, Utrecht, The Netherlands.ORCID 0000-0003-4324-5350
Sander BoymansCenter for Molecular Medicine and Oncode Institute, University Medical Center Utrecht, Utrecht, The Netherlands.ORCID 0000-0002-3517-2684
Jeroen de JongeErasmus Medical Center, Rotterdam, The Netherlands.
Jan N M IJzermansErasmus Medical Center, Rotterdam, The Netherlands.ORCID 0000-0003-3558-1039
Michail DoukasErasmus Medical Center, Rotterdam, The Netherlands.ORCID 0000-0002-8611-840X
Monique M A VerstegenErasmus Medical Center, Rotterdam, The Netherlands.
Ruben van BoxtelPrincess Máxima Center, Utrecht, The Netherlands.ORCID 0000-0003-1285-2836
Luc J W van der LaanErasmus Medical Center, Rotterdam, The Netherlands.ORCID 0000-0002-0651-5334
Edwin CuppenCenter for Molecular Medicine and Oncode Institute, University Medical Center Utrecht, Utrecht, The Netherlands. E.P.J.G.Cuppen@umcutrecht.nl.ORCID 0000-0002-0400-9542
Ewart KuijkCenter for Molecular Medicine and Oncode Institute, University Medical Center Utrecht, Utrecht, The Netherlands. e.w.kuijk-3@umcutrecht.nl.ORCID 0000-0002-1385-6516
University Medical Center Utrecht · NLErasmus MC · NLOncode Institute · NLPrincess Máxima Center · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Inflammatory liver disease increases the risk of developing primary liver cancer. The mechanism through which liver disease induces tumorigenesis remains unclear, but is thought to occur via increased mutagenesis. Here, we performed whole-genome sequencing on clonally expanded single liver stem cells cultured as intrahepatic cholangiocyte organoids (ICOs) from patients with alcoholic cirrhosis, non-alcoholic steatohepatitis (NASH), and primary sclerosing cholangitis (PSC). Surprisingly, we find that these precancerous liver disease conditions do not result in a detectable increased accumulation of mutations, nor altered mutation types in individual liver stem cells. This finding contrasts with the mutational load and typical mutational signatures reported for liver tumors, and argues against the hypothesis that liver disease drives tumorigenesis via a direct mechanism of induced mutagenesis. Disease conditions in the liver may thus act through indirect mechanisms to drive the transition from healthy to cancerous cells, such as changes to the microenvironment that favor the outgrowth of precancerous cells.

Indexed as

MutagenesisCholangitis, SclerosingHumansLiverLiver Cirrhosis, AlcoholicLiver DiseasesNon-alcoholic Fatty Liver DiseaseOrganoidsPrecancerous ConditionsStem Cells

Identifiers

PMID34795391
PMCPMC8602268
OpenAlexW3214580797

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.