Evidence map›Paper›PMID 29666172›Full record

ArticleGut2019

Genetic editing of colonic organoids provides a molecularly distinct and orthotopic preclinical model of serrated carcinogenesis.

Tamsin R M Lannagan, Young K Lee, Tongtong Wang, Jatin Roper, Mark L Bettington, Lochlan Fennell, Laura Vrbanac, Lisa Jonavicius, Roshini Somashekar, Krystyna Gieniec and 20 more

Abstract read
In one paragraph

Article in Gut, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed
7.8field-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

76 citing papers in PubMed, 137 citations in OpenAlex.

  1. Trial
  2. Article
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  5. Article
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  8. Beyond Rodents: Alternative Animal Models in Colorectal Cancer Research.International journal of molecular sciences · 2025
    Review
  9. BRAFiScience · 2025
    Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Next-Generation Modeling of Cancer Using Organoids.Cold Spring Harbor perspectives in medicine · 2024
    Review
  18. Article
  19. Article
  20. Article

16 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

30 authors at 15 institutions in 6 countries.

Tamsin R M LannaganSchool of Medicine, University of Adelaide and South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
Young K LeeSchool of Medicine, University of Adelaide and South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
Tongtong WangSchool of Medicine, University of Adelaide and South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
Jatin RoperThe David H. Koch Institute for Integrative Cancer Research at MIT, Cambridge, Massachusetts, USA.
Mark L BettingtonEnvoi Specialist Pathologists, Brisbane, Queensland, Australia.
Lochlan FennellConjoint Gastroenterology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Laura VrbanacSchool of Medicine, University of Adelaide and South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
Lisa JonaviciusDepartment of Anatomical Pathology, Flinders Medical Centre, Bedford Park, South Australia, Australia.
Roshini SomashekarSchool of Medicine, University of Adelaide and South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
Krystyna GieniecSchool of Medicine, University of Adelaide and South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
Miao YangSchool of Medicine, University of Adelaide and South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
Jia Q NgSchool of Medicine, University of Adelaide and South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
Nobumi SuzukiSchool of Medicine, University of Adelaide and South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
Mari IchinoseSchool of Medicine, University of Adelaide and South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
Josephine A WrightSchool of Medicine, University of Adelaide and South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
Hiroki KobayashiSchool of Medicine, University of Adelaide and South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
Tracey L PutoczkiDepartment of Medical Biology, University of Melbourne and the Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
Yoku HayakawaDepartment of Gastroenterology, University of Tokyo, Tokyo, Japan.ORCID 0000-0002-3988-2499
Simon J LeedhamTranslational Gastroenterology Unit, Experimental Medicine Division, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, UK.
Helen E AbudCancer Program, Monash Biomedicine Discovery Institute and the Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.
Ömer H YilmazThe David H. Koch Institute for Integrative Cancer Research at MIT, Cambridge, Massachusetts, USA.
Julie MarkerCancer Voices SA, Adelaide, South Australia, Australia.
Sonja KlebeDepartment of Anatomical Pathology, Flinders Medical Centre, Bedford Park, South Australia, Australia.
Pratyaksha WirapatiBioinformatics Core Facility, Swiss Institute of Bioinformatics, Lausanne, Switzerland.
Siddhartha MukherjeeDepartment of Medicine, Columbia University Medical Center, New York City, New York, USA.
Sabine TejparDigestive Oncology Unit, Department of Oncology, University Hospitals Leuven, Leuven, Belgium.
Barbara A LeggettConjoint Gastroenterology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Vicki L J WhitehallConjoint Gastroenterology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Daniel L Worthley *School of Medicine, University of Adelaide and South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
Susan L Woods *School of Medicine, University of Adelaide and South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.ORCID 0000-0002-8955-2017
South Australian Health and Medical Research Institute · AUFlinders Medical Centre · AUCentre for Human Genetics · GBColumbia University Irving Medical Center · USDiscovery Institute · USMassachusetts General Hospital · USMolecular Oncology (United States) · USQIMR Berghofer Medical Research Institute · AUQueensland Health · AUSIB Swiss Institute of Bioinformatics · CHThe University of Melbourne · AUThe University of Queensland · AUThe University of Tokyo · JPTufts Medical Center · USUniversity of the Sunshine Coast · AU

Funding

Women's Cancer Research ProgramP30CA014236 · NCI · DUKE UNIVERSITY · PI JOHN N. NORTON · 1985 to 2026
$174.8M
VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Jacqueline A. Lees · 1985 to 2026
$93.9M
Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG · 1991 to 2026
$35.3M
Understanding and Improving Platinum Anticancer DrugsR01CA034992 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI YILMAZ, OMER · 1985 to 2018
$6.8M
Dietary control of stem cells in physiology and cancerR01CA211184 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI YILMAZ, OMER · 2017 to 2021
$2.0M
The role of Mtss1 in Hedgehog-mediated intestinal cancer stem cell functionK08CA198002 · NCI · TUFTS MEDICAL CENTER · PI ROPER, JATIN · 2015 to 2019
$845k
Regulation of the Intestinal Stem Cell Niche in AgingR00AG045144 · NIA · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI YILMAZ, OMER · 2014 to 2016
$740k
Real-time in Vivo Dosimetry in Radiation Therapy Using Scintillation DetectorsR01CA120198 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BEDDAR, SAM · 2007 to 2009
$578k
Cancer Research UK 16581NCI NIH HHS K08 CA198002NCI NIH HHS P30 CA014051NCI NIH HHS P30 CA014236NCI NIH HHS R01 CA034992NCI NIH HHS R01 CA120198NCI NIH HHS R01 CA211184NIA NIH HHS R00 AG045144NIDDK NIH HHS P30 DK043351Wellcome Trust 206314/Z/17/Z
6 · The paper itself

Abstract

objectiveSerrated colorectal cancer (CRC) accounts for approximately 25% of cases and includes tumours that are among the most treatment resistant and with worst outcomes. This CRC subtype is associated with activating mutations in the mitogen-activated kinase pathway gene,

designWe use organoid culture combined with CRISPR/Cas9 genome engineering to sequentially introduce genetic alterations associated with serrated CRC and which regulate the stem cell niche, senescence and DNA mismatch repair.

resultsTargeted biallelic gene alterations were verified by DNA sequencing. Organoid growth in the absence of niche factors was assessed, as well as analysis of downstream molecular pathway activity. Orthotopic engraftment of complex organoid lines, but not

conclusionWe generate rapid, complex models of serrated CRC to determine the contribution of specific genetic alterations to carcinogenesis. Analysis of our models alongside patient data has led to the identification of a potential susceptibility for this tumour type.

Indexed as

AdenocarcinomaAllelesColonColorectal NeoplasmsCpG IslandsDisease ProgressionDNA Mismatch RepairDNA Mutational AnalysisEpigenomicsGene Expression Regulation, NeoplasticGenes, Tumor SuppressorHumansModels, GeneticMutationOrganoidsPhenotypeBRAF protein, humanProto-Oncogene Proteins B-rafcancer geneticscolorectal cancergene mutationmethylationoncogenes

Identifiers

PMID29666172
PMCPMC6192855
OpenAlexW2606042026

What OpenQuestion holds

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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.