Evidence map›Paper›PMID 27659016›Full record

ArticleNeoplasia (New York, N.Y.)2016

Hypoxia-Inducible Factor 2α Mutation-Related Paragangliomas Classify as Discrete Pseudohypoxic Subcluster.

Stephanie M J Fliedner, Uma Shankavaram, Geena Marzouca, Abdel Elkahloun, Ivana Jochmanova, Roland Daerr, W Marston Linehan, Henri Timmers, Arthur S Tischler, Konstantinos Papaspyrou and 7 more

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

Article in Neoplasia (New York, N.Y.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
1.0field-weighted citation impact, top 24% 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

13 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.

  1. Pooled it
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  6. Metastatic Paraganglioma of the Spine WithInternational journal of spine surgery · 2021
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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

17 authors at 12 institutions in 4 countries.

Stephanie M J Fliedner1st Department of Medicine, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany; Section of Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. Electronic address: stephanie.fliedner@uksh.de.
Uma ShankavaramRadiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Geena MarzoucaSection of Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Abdel ElkahlounCancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Ivana JochmanovaSection of Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA; 1st Department of Internal Medicine Medical Faculty of P. J. Šafárik University in Košice, Košice, Slovakia.
Roland DaerrSection of Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA; Institute of Clinical Chemistry & Laboratory Medicine and Department of Medicine III, University Hospital Carl Gustav Carus, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
W Marston LinehanUrologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Henri TimmersDepartment of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
Arthur S TischlerTufts Medical Center, Boston, MA, USA.
Konstantinos PapaspyrouDepartment of Otorhinolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
Jürgen BriegerDepartment of Otorhinolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
Ronald de KrijgerDepartment of Pathology, Josephine Nefkens Institute, Erasmus MC-University Medical Center, Rotterdam, The Netherlands; Department of Pathology, Reinier de Graaf Hospital, Delft, The Netherlands.
Jan BrezaDepartment of Urology, Comenius University, Bratislava, Slovak Republic.
Graeme EisenhoferInstitute of Clinical Chemistry & Laboratory Medicine and Department of Medicine III, University Hospital Carl Gustav Carus, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Zhengping ZhuangSurgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Hendrik Lehnert1st Department of Medicine, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
Karel PacakSection of Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. Electronic address: karel.pacak@nih.gov.
National Institutes of Health · USUniversity Medical Center of the Johannes Gutenberg University Mainz · DEUniversity of Lübeck · DEComenius University Bratislava · SKErasmus MC · NLNational Cancer Institute · USNational Institute of Neurological Disorders and Stroke · USRadboud University Medical Center · NLTU Dresden · DETufts Medical Center · USUniversity Hospital Carl Gustav Carus · DEUniversity of Pavol Jozef Šafárik · SK

Funding

Diagnosis, Pathophysiology And Molecular Biology of Pheochromocytoma and ParagangliomaZIAHD008735 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI PACAK, KAREL · 2009 to 2024
$28.4M
6 · The paper itself

Abstract

Recently, activating mutations of the hypoxia-inducible factor 2α gene (HIF2A/EPAS1) have been recognized to predispose to multiple paragangliomas (PGLs) and duodenal somatostatinomas associated with polycythemia, and ocular abnormalities. Previously, mutations in the SDHA/B/C/D, SDHAF2, VHL, FH, PHD1, and PHD2 genes have been associated with HIF activation and the development of pseudohypoxic (cluster-1) PGLs. These tumors overlap in terms of tumor location, syndromic presentation, and noradrenergic phenotype to a certain extent. However, they also differ especially by clinical outcome and by presence of other tumors or abnormalities. In the present study, we aimed to establish additional molecular differences between HIF2A and non-HIF2A pseudohypoxic PGLs. RNA expression patterns of HIF2A PGLs (n=6) from 2 patients were compared with normal adrenal medullas (n=8) and other hereditary pseudohypoxic PGLs (VHL: n=13, SDHB: n=15, and SDHD: n=14). Unsupervised hierarchical clustering showed that HIF2A PGLs made up a separate cluster from other pseudohypoxic PGLs. Significance analysis of microarray yielded 875 differentially expressed genes between HIF2A and other pseudohypoxic PGLs after normalization to adrenal medulla (false discovery rate 0.01). Prediction analysis of microarray allowed correct classification of all HIF2A samples based on as little as three genes (TRHDE, LRRC63, IGSF10; error rate: 0.02). Genes with the highest expression difference between normal medulla and HIF2A PGLs were selected for confirmatory quantitative reverse transcriptase polymerase chain reaction. In conclusion, HIF2A PGLs show a characteristic expression signature that separates them from non-HIF2A pseudohypoxic PGLs. Unexpectedly, the most significantly differentially expressed genes have not been previously described as HIF target genes.

Indexed as

MutationAdolescentAdultAgedBasic Helix-Loop-Helix ProteinsChildCluster AnalysisEndothelial PAS Domain-Containing Protein 1FemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansHypoxiaMaleMiddle AgedOxidative PhosphorylationBasic Helix-Loop-Helix ProteinsEndothelial PAS Domain-Containing Protein 1

Identifiers

PMID27659016
PMCPMC5031903
OpenAlexW2523635309

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.