Evidence map›Paper›PMID 40410286›Full record

ArticleScientific reports2025

Small intestinal neuroendocrine tumors lack early genomic drivers, acquire DNA repair defects and harbor hallmarks of low REST expression.

Felix Bolduan, Niklas Müller-Bötticher, Olivia Debnath, Ines Eichhorn, Yvonne Giesecke, Alexandra Wetzel, Shashwat Sahay, Tomasz Zemojtel, Marten Jaeger, Ute Ungethuem and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

19 authors.

Felix Bolduan *Department of Hepatology & Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, 13353, Berlin, Germany.
Niklas Müller-Bötticher *Center of Digital Health, Berlin Institute of Health at Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Olivia DebnathCenter of Digital Health, Berlin Institute of Health at Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Ines EichhornDepartment of Hepatology & Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, 13353, Berlin, Germany.
Yvonne GieseckeDepartment of Hepatology & Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, 13353, Berlin, Germany.
Alexandra WetzelDepartment of Hepatology & Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, 13353, Berlin, Germany.
Shashwat SahayCenter of Digital Health, Berlin Institute of Health at Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Tomasz ZemojtelCore Facility Genomics, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Marten JaegerCore Facility Genomics, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Ute UngethuemCore Facility Genomics, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Christoph RoderburgDepartment of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Catarina Alisa KunzeInstitute of Pathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, 10117, Berlin, Germany.
Annika LehmannInstitute of Pathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, 10117, Berlin, Germany.
David HorstInstitute of Pathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, 10117, Berlin, Germany.
Frank TackeDepartment of Hepatology & Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, 13353, Berlin, Germany.
Roland EilsCenter of Digital Health, Berlin Institute of Health at Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Bertram Wiedenmann *Department of Hepatology & Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, 13353, Berlin, Germany. bertram.wiedenmann@charite.de.
Michael Sigal *Department of Hepatology & Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, 13353, Berlin, Germany. michael.sigal@charite.de.
Naveed Ishaque *Center of Digital Health, Berlin Institute of Health at Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany. naveed.ishaque@bih-charite.de.ORCID http://orcid.org/0000-0002-8426-901X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The tumorigenesis of small intestinal neuroendocrine tumors (siNETs) is not understood and comprehensive genomic and transcriptomic data sets are limited. Therefore, we performed whole genome and transcriptome analysis of 39 well differentiated siNET samples. Our genomic data revealed a lack of recurrent driver mutations and demonstrated that multifocal siNETs from individual patients can arise genetically independently. We detected germline mutations in Fanconi anemia DNA repair pathway (FANC) genes, involved in homologous recombination (HR) DNA repair, in 9% of patients and found mutational signatures of defective HR DNA repair in late-stage tumor evolution. Furthermore, transcriptomic analysis revealed low expression of the transcriptional repressor REST. Summarizing, we identify a novel common transcriptomic signature of siNETs and demonstrate that genomic alterations alone do not explain initial tumor formation, while impaired DNA repair likely contributes to tumor evolution and represents a potential pharmaceutical target in a subset of patients.

Indexed as

DNA RepairIntestinal NeoplasmsIntestine, SmallNeuroendocrine TumorsRepressor ProteinsAdultFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGenomicsGerm-Line MutationHumansMaleMiddle AgedTranscriptomeRepressor Proteins

Identifiers

PMID40410286
PMCPMC12102166

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Registered trials

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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.