Evidence map›Paper›PMID 26780541›Full record

ArticleFamilial cancer2016

Exome sequencing identifies potential novel candidate genes in patients with unexplained colorectal adenomatous polyposis.

Isabel Spier, Martin Kerick, Dmitriy Drichel, Sukanya Horpaopan, Janine Altmüller, Andreas Laner, Stefanie Holzapfel, Sophia Peters, Ronja Adam, Bixiao Zhao and 10 more

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Familial cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 1 pooled it
7.1field-weighted citation impact, top 2% 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

33 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Open biology · 2025
    Review
  5. Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Review
  11. Review
  12. Novel Genetic Causes of Gastrointestinal Polyposis Syndromes.The application of clinical genetics · 2021
    Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
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

20 authors at 9 institutions in 4 countries.

Isabel SpierInstitute of Human Genetics, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany. isabel.spier@uni-bonn.de.
Martin KerickDepartment of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Dmitriy DrichelGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Sukanya HorpaopanInstitute of Human Genetics, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
Janine AltmüllerCologne Center for Genomics (CCG), University of Cologne, Cologne, Germany.
Andreas LanerMedizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München, Munich, Germany.
Stefanie HolzapfelInstitute of Human Genetics, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
Sophia PetersInstitute of Human Genetics, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
Ronja AdamInstitute of Human Genetics, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
Bixiao ZhaoDepartments of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT, USA.
Tim BeckerGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Richard P LiftonDepartments of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT, USA.
Elke Holinski-FederMedizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München, Munich, Germany.
Sven PernerSection for Prostate Cancer Research, Center for Integrated Oncology Cologne/Bonn, Institute of Pathology, University Hospital of Bonn, Bonn, Germany.
Holger ThieleCologne Center for Genomics (CCG), University of Cologne, Cologne, Germany.
Markus M NöthenInstitute of Human Genetics, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
Per HoffmannInstitute of Human Genetics, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
Bernd TimmermannNext Generation Sequencing Group, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Michal R SchweigerDepartment of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Stefan AretzInstitute of Human Genetics, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
University of Bonn · DEUniversity of Cologne · DEMax Planck Institute for Molecular Genetics · DEYale University · USGerman Center for Neurodegenerative Diseases · DEInstitut für Medizinische Biometrie, Informatik und Epidemiologie · DELMU Klinikum · DEMedical Genetics Center · DEUniversity Hospital Bonn · DE

Funding

Yale Center for Mendelian DisordersU54HG006504 · NHGRI · YALE UNIVERSITY · PI GERSTEIN, MARK BENDER, GUNEL, MURAT · 2012 to 2015
$11.0M
NHGRI NIH HHS 5U54HG006504
6 · The paper itself

Abstract

In up to 30% of patients with colorectal adenomatous polyposis, no germline mutation in the known genes APC, causing familial adenomatous polyposis, MUTYH, causing MUTYH-associated polyposis, and POLE or POLD1, causing Polymerase-Proofreading-associated polyposis can be identified, although a hereditary etiology is likely. To uncover new causative genes, exome sequencing was performed using DNA from leukocytes and a total of 12 colorectal adenomas from seven unrelated patients with unexplained sporadic adenomatous polyposis. For data analysis and variant filtering, an established bioinformatics pipeline including in-house tools was applied. Variants were filtered for rare truncating point mutations and copy-number variants assuming a dominant, recessive, or tumor suppressor model of inheritance. Subsequently, targeted sequence analysis of the most promising candidate genes was performed in a validation cohort of 191 unrelated patients. All relevant variants were validated by Sanger sequencing. The analysis of exome sequencing data resulted in the identification of rare loss-of-function germline mutations in three promising candidate genes (DSC2, PIEZO1, ZSWIM7). In the validation cohort, further variants predicted to be pathogenic were identified in DSC2 and PIEZO1. According to the somatic mutation spectra, the adenomas in this patient cohort follow the classical pathways of colorectal tumorigenesis. The present study identified three candidate genes which might represent rare causes for a predisposition to colorectal adenoma formation. Especially PIEZO1 (FAM38A) and ZSWIM7 (SWS1) warrant further exploration. To evaluate the clinical relevance of these genes, investigation of larger patient cohorts and functional studies are required.

Indexed as

ExomeAdenomatous Polyposis ColiAdenomatous PolypsAgedDesmocollinsFemaleGenetic Predisposition to DiseaseGerm-Line MutationHigh-Throughput Nucleotide SequencingHumansIon ChannelsMaleMiddle AgedReproducibility of ResultsDesmocollinsDSC2 protein, humanIon ChannelsPIEZO1 protein, humanAdenomatous polyposisCandidate genesExome sequencingFamilial colorectal cancerHereditary tumor syndromesMassive parallel sequencing

Identifiers

PMID26780541
OpenAlexW2265018649

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.