Evidence map›Paper›PMID 30229897›Full record

ArticleInternational journal of cancer2019

Single-cell genetic analysis of clonal dynamics in colorectal adenomas indicates CDX2 gain as a predictor of recurrence.

David Fiedler, Kerstin Heselmeyer-Haddad, Daniela Hirsch, Leanora S Hernandez, Irianna Torres, Darawalee Wangsa, Yue Hu, Luis Zapata, Josef Rueschoff, Sebastian Belle and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in International journal of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

11 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Chromatin Mechanisms Driving Cancer.Cold Spring Harbor perspectives in biology · 2022
    Review
  7. Review
  8. Article
  9. Single-Cell-Derived Primary Rectal Carcinoma Cell Lines Reflect Intratumor Heterogeneity Associated with Treatment Response.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020
    Article
  10. Article
  11. 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

12 authors at 4 institutions in 4 countries.

David FiedlerInstitute of Pathology, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Kerstin Heselmeyer-HaddadGenetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Daniela HirschInstitute of Pathology, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Leanora S HernandezGenetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Irianna TorresGenetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Darawalee WangsaGenetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Yue HuGenetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Luis ZapataCentre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom.
Josef RueschoffInstitute of Pathology Nordhessen, Kassel, Germany.
Sebastian BelleDepartment of Internal Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Thomas RiedGenetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.ORCID 0000-0002-0767-6009
Timo GaiserInstitute of Pathology, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.ORCID 0000-0002-6022-073X
National Institutes of Health · USHeidelberg University · DEInstitute of Cancer Research · GBUniversity of Kassel · DE

Funding

Prediction of Therapy Response in Colorectal CancerZIABC010837 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI RIED, THOMAS · 2009 to 2022
$8.9M
Identification and functional characterization of colorectal cancer genesZ01BC010833 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI RIED, THOMAS · 2007 to 2008
$1.5M
Intramural NIH HHS Z01 BC010833
6 · The paper itself

Abstract

Colorectal adenomas are common precancerous lesions with the potential for malignant transformation to colorectal adenocarcinoma. Endoscopic polypectomy provides an opportunity for cancer prevention; however, recurrence rates are high. We collected formalin-fixed paraffin-embedded tissue of 15 primary adenomas with recurrence, 15 adenomas without recurrence, and 14 matched pair samples (primary adenoma and the corresponding recurrent adenoma). The samples were analysed by array-comparative genomic hybridisation (aCGH) and single-cell multiplex interphase fluorescence in situ hybridisation (miFISH) to understand clonal evolution, to examine the dynamics of copy number alterations (CNAs) and to identify molecular markers for recurrence prediction. The miFISH probe panel consisted of 14 colorectal carcinogenesis-relevant genes (COX2, PIK3CA, APC, CLIC1, EGFR, MYC, CCND1, CDX2, CDH1, TP53, HER2, SMAD7, SMAD4 and ZNF217), and a centromere probe (CEP10). The aCGH analysis confirmed the genetic landscape typical for colorectal tumorigenesis, that is, CNAs of chromosomes 7, 13q, 18 and 20q. Focal aberrations (≤10 Mbp) were mapped to chromosome bands 6p22.1-p21.33 (33.3%), 7q22.1 (31.4%) and 16q21 (29.4%). MiFISH detected gains of EGFR (23.6%), CDX2 (21.8%) and ZNF217 (18.2%). Most adenomas exhibited a major clone population which was accompanied by multiple smaller clone populations. Gains of CDX2 were exclusively seen in primary adenomas with recurrence (25%) compared to primary adenomas without recurrence (0%). Generation of phylogenetic trees for matched pair samples revealed four distinct patterns of clonal dynamics. In conclusion, adenoma development and recurrence are complex genetic processes driven by multiple CNAs whose evaluations by miFISH, with emphasis on CDX2, might serve as a predictor of recurrence.

Indexed as

AdenomaAgedBiomarkers, TumorCDX2 Transcription FactorChromosome AberrationsClonal EvolutionColorectal NeoplasmsComparative Genomic HybridizationDNA Copy Number VariationsFemaleHumansIn Situ Hybridization, FluorescenceMaleMiddle AgedNeoplasm Recurrence, LocalSingle-Cell AnalysisBiomarkers, TumorCDX2 protein, humanCDX2 Transcription FactorCDX2clonal evolutioncolorectal adenomaFISHgenomic instabilityintratumour heterogeneityrecurrence

Identifiers

PMID30229897
PMCPMC6361680
OpenAlexW2891036706

What OpenQuestion holds

Textmetadata
LicenceTDM
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.