Evidence map›Paper›PMID 38124114›Full record

ArticleClinical epigenetics2023

A comprehensive characterisation of phaeochromocytoma and paraganglioma tumours through histone protein profiling, DNA methylation and transcriptomic analysis genome wide.

Prodromos Chatzikyriakou, Dimitria Brempou, Mark Quinn, Lauren Fishbein, Roberta Noberini, Ioannis N Anastopoulos, Nicola Tufton, Eugenie S Lim, Rupert Obholzer, Johnathan G Hubbard and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical epigenetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the 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
4.4field-weighted citation impact, top 5% 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

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.

  1. Pooled it
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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

15 authors at 8 institutions in 3 countries.

Prodromos ChatzikyriakouDepartment of Medical and Molecular Genetics, King's College London, London, SE1 9RT, UK.
Dimitria BrempouDepartment of Medical and Molecular Genetics, King's College London, London, SE1 9RT, UK.
Mark QuinnDepartment of Medical and Molecular Genetics, King's College London, London, SE1 9RT, UK.
Lauren FishbeinDivision of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Roberta NoberiniDepartment of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Via Adamello 16, 20139, Milan, Italy.
Ioannis N AnastopoulosDepartment of Biomolecular Engineering, UC Santa Cruz Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA, 95064, USA.
Nicola TuftonDepartment of Endocrinology, St. Bartholomew's Hospital, Barts Health NHS Trust, and William Harvey Research Institute, Queen Mary University of London, London, UK.
Eugenie S LimDepartment of Endocrinology, St. Bartholomew's Hospital, Barts Health NHS Trust, and William Harvey Research Institute, Queen Mary University of London, London, UK.
Rupert ObholzerDepartment of ENT and Skull Base Surgery, Guy's and St Thomas' NHS Foundation Trust, London, SE1 9RT, UK.
Johnathan G HubbardDepartment of Endocrine Surgery, Guy's and St Thomas' NHS Foundation Trust, London, SE1 9RT, UK.
Mufaddal MoonimDepartment of Cellular Pathology, Guy's and St Thomas' NHS Foundation Trust, London, SE1 9RT, UK.
Tiziana BonaldiDepartment of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Via Adamello 16, 20139, Milan, Italy.
Katherine L NathansonDivision of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Louise IzattDepartment of Clinical Genetics, Guy's and St Thomas' NHS Foundation Trust, London, SE1 9RT, UK.
Rebecca J OakeyDepartment of Medical and Molecular Genetics, King's College London, London, SE1 9RT, UK. rebecca.oakey@kcl.ac.uk.
Guy's and St Thomas' NHS Foundation Trust · GBKing's College London · GBEuropean Institute of Oncology · ITAbramson Cancer CenterQueen Mary University of London · GBSt Bartholomew's Hospital · GBUniversity of California, Santa Cruz · USUniversity of Pennsylvania · US

Funding

Investigating the association between the somatic and inherited genetics of pheocR21CA185953 · NCI · UNIVERSITY OF PENNSYLVANIA · PI NATHANSON, KATHERINE L. · 2014 to 2015
$361k
Medical Research Council MC_PC_17164Medical Research Council MR/W001101/1NCI NIH HHS R21 CA185953NIH HHS CA185953Wellcome TrustWellcome Trust 212917/Z/18/Z
6 · The paper itself

Abstract

backgroundPhaeochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours. Pathogenic variants have been identified in more than 15 susceptibility genes; associated tumours are grouped into three Clusters, reinforced by their transcriptional profiles. Cluster 1A PPGLs have pathogenic variants affecting enzymes of the tricarboxylic acid cycle, including succinate dehydrogenase. Within inherited PPGLs, these are the most common. PPGL tumours are known to undergo epigenetic reprograming, and here, we report on global histone post-translational modifications and DNA methylation levels, alongside clinical phenotypes.

resultsOut of the 25 histone post-translational modifications examined, Cluster 1A PPGLs were distinguished from other tumours by a decrease in hyper-acetylated peptides and an increase in H3K4me2. DNA methylation was compared between tumours from individuals who developed metastatic disease versus those that did not. The majority of differentially methylated sites identified tended to be completely methylated or unmethylated in non-metastatic tumours, with low inter-sample variance. Metastatic tumours by contrast consistently had an intermediate DNA methylation state, including the ephrin receptor EPHA4 and its ligand EFNA3. Gene expression analyses performed to identify genes involved in metastatic tumour behaviour pin-pointed a number of genes previously described as mis-regulated in Cluster 1A tumours, as well as highlighting the tumour suppressor RGS22 and the pituitary tumour-transforming gene PTTG1.

conclusionsCombined transcriptomic and DNA methylation analyses revealed aberrant pathways, including ones that could be implicated in metastatic phenotypes and, for the first time, we report a decrease in hyper-acetylated histone marks in Cluster 1 PPGLs.

Indexed as

Adrenal Gland NeoplasmsParagangliomaPheochromocytomaDNA MethylationGene Expression ProfilingHistonesHumansHistonesCancer predispositionDNA methylationEpigeneticsGermline pathogenic variantHistone post-translational modificationsMass spectrometryParagangliomaPhaeochromocytomaSDHSuccinate dehydrogenase

Identifiers

PMID38124114
PMCPMC10734084
OpenAlexW4389993400

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.