Evidence map›Paper›PMID 27029034›Full record

Trial reportOncotarget2016

Dynamic epigenetic changes to VHL occur with sunitinib in metastatic clear cell renal cancer.

Grant D Stewart, Thomas Powles, Christophe Van Neste, Alison Meynert, Fiach O'Mahony, Alexander Laird, Dieter Deforce, Filip Van Nieuwerburgh, Geert Trooskens, Wim Van Criekinge and 2 more

Registry-linked trialOpen access · diamondAbstract readClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01024205 (Upfront Sunitinib), which is not on this map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 11% 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.

NCT01024205 phase2completednot on this map

Upfront Sunitinib (SU011248) Therapy Followed by Surgery in Patients With Metastatic Renal Cancer: A Pilot Phase II Study [SuMR]

TypeinterventionalSponsorBarts and the London School of Medicine and DentistryRan2007 to 2012Enrolled43ConditionsKidney CancerArmssunitinib malate, laboratory biomarker analysis, adjuvant therapy, neoadjuvant therapy, therapeutic conventional surgery
3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. The Role of DNA Methylation in Renal Cell Carcinoma.Molecular diagnosis & therapy · 2018
    Review
  9. Review
  10. 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 6 institutions in 2 countries.

Grant D StewartEdinburgh Urological Cancer Group, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Thomas PowlesRenal Cancer Unit, The Royal Free Hospital, London, UK.
Christophe Van NesteLaboratory of Pharmaceutical Biotechnology, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
Alison MeynertMRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Fiach O'MahonyEdinburgh Urological Cancer Group, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Alexander LairdEdinburgh Urological Cancer Group, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Dieter DeforceLaboratory of Pharmaceutical Biotechnology, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
Filip Van NieuwerburghLaboratory of Pharmaceutical Biotechnology, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
Geert TrooskensBiobix: Laboratory of Bioinformatics and Computational Genomics, Department of Mathematical Modeling, Statistics and Bioinformatics, Ghent University, Ghent, Belgium.
Wim Van CriekingeBiobix: Laboratory of Bioinformatics and Computational Genomics, Department of Mathematical Modeling, Statistics and Bioinformatics, Ghent University, Ghent, Belgium.
Tim De MeyerBiobix: Laboratory of Bioinformatics and Computational Genomics, Department of Mathematical Modeling, Statistics and Bioinformatics, Ghent University, Ghent, Belgium.
David J HarrisonScottish Collaboration On Translational Research into Renal Cell Cancer (SCOTRRCC), Scotland, UK.
Ghent University · BEEdinburgh Cancer Research · GBMRC Institute of Genetics and Molecular Medicine · GBThe Royal Free Hospital · GBUniversity of Cambridge · GBUniversity of St Andrews · GB

Funding

Wellcome Trust
6 · The paper itself

Abstract

backgroundGenetic intratumoral heterogeneity (ITH) hinders biomarker development in metastatic clear cell renal cancer (mccRCC). Epigenetic relative to genetic ITH or the presence of consistent epigenetic changes following targeted therapy in mccRCC have not been evaluated. The aim of this study was to determine methylome/genetic ITH and to evaluate specific epigenetic and genetic changes associated with sunitinib therapy. PATIENTS AND

methodsMulti-region DNA sampling performed on sequential frozen pairs of primary tumor tissue from 14 metastatic ccRCC patients, in the Upfront Sunitinib (SU011248) Therapy Followed by Surgery in Patients with Metastatic Renal Cancer: a Pilot Phase II Study (SuMR; ClinicalTrials.gov identifier: NCT01024205), at presentation (biopsy) and after 3-cycles of 50mg sunitinib (nephrectomy). Untreated biopsy and nephrectomy samples before and after renal artery ligation were controls. Ion Proton sequencing of 48 key ccRCC genes, and MethylCap-seq DNA methylation analysis was performed, data was analysed using the statistical computing environment R.

resultsUnsupervised hierarchical clustering revealed complete methylome clustering of biopsy and three nephrectomy samples for each patient (14/14 patients). For mutational status, untreated biopsy and all treated nephrectomy samples clustered together in 8/13 (61.5%) patients. The only methylation target significantly altered following sunitinib therapy was VHL promoter region 7896829 which was hypermethylated with treatment (FDR=0.077, P<0.001) and consistent for all patients (pre-treatment 50% patients had VHL mutations, 14% patients VHL hypermethylation). Renal artery ligation did not affect this result. No significant differences in driver or private mutation count was found with sunitinib treatment.

conclusionsDemonstration of relative methylome homogeneity and consistent VHL hypermethylation, after sunitinib, may overcome the hurdle of ITH present at other molecular levels for biomarker research.

Indexed as

Antineoplastic AgentsCarcinoma, Renal CellCluster AnalysisDNA MethylationDNA Mutational AnalysisEpigenesis, GeneticFemaleHumansIndolesKidney NeoplasmsMaleMiddle AgedPilot ProjectsPromoter Regions, GeneticPyrrolesSunitinibAntineoplastic AgentsIndolesPyrrolesSunitinibVHL protein, humanVon Hippel-Lindau Tumor Suppressor Proteinheterogeneitymethylationmutationsrenal cancerVHL

Identifiers

PMID27029034
PMCPMC5041900
OpenAlexW2308085377

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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.