Evidence map›Paper›PMID 25587359›Full record

ArticleGenome medicine2014

Assessment of patient-derived tumour xenografts (PDXs) as a discovery tool for cancer epigenomics.

Paul Guilhamon, Lee M Butcher, Nadege Presneau, Gareth A Wilson, Andrew Feber, Dirk S Paul, Moritz Schütte, Johannes Haybaeck, Ulrich Keilholz, Jens Hoffman and 3 more

Abstract read
In one paragraph

Article in Genome medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing 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

20 citing papers in PubMed.

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  18. Neuroblastoma, a Paradigm for Big Data Science in Pediatric Oncology.International journal of molecular sciences · 2016
    Review
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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

13 authors.

Paul GuilhamonMedical Genomics, UCL Cancer Institute, University College London, London, WC1E 6DD UK.
Lee M ButcherMedical Genomics, UCL Cancer Institute, University College London, London, WC1E 6DD UK.
Nadege PresneauGenetics and Cell Biology of Sarcoma, UCL Cancer Institute, University College London, London, WC1E 6DD UK ; Department of Biomedical Sciences, University of Westminster, London, W1W 6UW UK.
Gareth A WilsonMedical Genomics, UCL Cancer Institute, University College London, London, WC1E 6DD UK ; Translational Cancer Therapeutics Laboratory, CR-UK London Research Institute, London, WC2A 3LY UK.
Andrew FeberMedical Genomics, UCL Cancer Institute, University College London, London, WC1E 6DD UK.
Dirk S PaulMedical Genomics, UCL Cancer Institute, University College London, London, WC1E 6DD UK.
Moritz SchütteAlacris Theranostics GmbH, 14195 Berlin, Germany.
Johannes HaybaeckInstitute of Pathology, Medical University of Graz, 8036 Graz, Austria.
Ulrich KeilholzDepartment of Hematology and Medical Oncology, Charité Comprehensive Cancer Center, D-10117 Berlin, Germany.
Jens HoffmanEPO-Berlin-Buch GmbH, 13125 Berlin, Germany.
Mark T RossIllumina Cambridge Ltd, Chesterford Research Park, Little Chesterford, CB10 1XL UK.
Adrienne M FlanaganGenetics and Cell Biology of Sarcoma, UCL Cancer Institute, University College London, London, WC1E 6DD UK ; Department of Histopathology, Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex, London, HA7 4LP UK.
Stephan BeckMedical Genomics, UCL Cancer Institute, University College London, London, WC1E 6DD UK.

Funding

British Heart Foundation RG/08/014/24067Medical Research Council MR/L003120/1Wellcome Trust
6 · The paper itself

Abstract

backgroundThe use of tumour xenografts is a well-established research tool in cancer genomics but has not yet been comprehensively evaluated for cancer epigenomics.

methodsIn this study, we assessed the suitability of patient-derived tumour xenografts (PDXs) for methylome analysis using Infinium 450 K Beadchips and MeDIP-seq.

resultsControlled for confounding host (mouse) sequences, comparison of primary PDXs and matching patient tumours in a rare (osteosarcoma) and common (colon) cancer revealed that an average 2.7% of the assayed CpG sites undergo major (Δβ ≥ 0.51) methylation changes in a cancer-specific manner as a result of the xenografting procedure. No significant subsequent methylation changes were observed after a second round of xenografting between primary and secondary PDXs. Based on computational simulation using publically available methylation data, we additionally show that future studies comparing two groups of PDXs should use 15 or more samples in each group to minimise the impact of xenografting-associated changes in methylation on comparison results.

conclusionsOur results from rare and common cancers indicate that PDXs are a suitable discovery tool for cancer epigenomics and we provide guidance on how to overcome the observed limitations.

Identifiers

PMID25587359
PMCPMC4292812

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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.