Evidence map›Paper›PMID 40097403›Full record

ArticleNature communications2025

Multi-omic analysis of SDHB-deficient pheochromocytomas and paragangliomas identifies metastasis and treatment-related molecular profiles.

Aidan Flynn, Andrew D Pattison, Shiva Balachander, Emma Boehm, Blake Bowen, Trisha Dwight, Fernando J Rossello, Oliver Hofmann, Luciano Martelotto, Maia Zethoven and 24 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
–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

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

  1. Pooled it
  2. Review
  3. Article
  4. Genetic alterations of telomere maintenance pathways in paragangliomas.Archives of endocrinology and metabolism · 2026
    Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. The evolving roles of pathologists in paragangliomas and pheochromocytomas.Virchows Archiv : an international journal of pathology · 2026
    Review
  14. Approach to the Patient With Metastatic Pheochromocytoma and Paraganglioma.The Journal of clinical endocrinology and metabolism · 2025
    Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Non-Susceptibility Gene Variants in Head and Neck Paragangliomas.International journal of molecular sciences · 2024
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

34 authors.

Aidan FlynnCentre for Cancer Research and Department of Clinical Pathology, University of Melbourne, VIC, Australia.
Andrew D PattisonCentre for Cancer Research and Department of Clinical Pathology, University of Melbourne, VIC, Australia.
Shiva BalachanderCentre for Cancer Research and Department of Clinical Pathology, University of Melbourne, VIC, Australia.
Emma BoehmCentre for Cancer Research and Department of Clinical Pathology, University of Melbourne, VIC, Australia.
Blake BowenCentre for Cancer Research and Department of Clinical Pathology, University of Melbourne, VIC, Australia.
Trisha DwightKolling Institute of Medical Research, Royal North Shore Hospital St Leonards NSW, Melbourne, Australia.
Fernando J RosselloCentre for Cancer Research and Department of Clinical Pathology, University of Melbourne, VIC, Australia.
Oliver HofmannCentre for Cancer Research and Department of Clinical Pathology, University of Melbourne, VIC, Australia.
Luciano MartelottoCentre for Cancer Research and Department of Clinical Pathology, University of Melbourne, VIC, Australia.ORCID http://orcid.org/0000-0002-9625-1183
Maia ZethovenPeter MacCallum Cancer Centre, Melbourne, Australia.ORCID http://orcid.org/0000-0002-6528-891X
Lawrence S KirschnerDivision of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.ORCID http://orcid.org/0000-0001-6180-342X
Tobias ElseUniversity of Michigan, Ann Arbor, MI, USA.
Lauren FishbeinDepartment of Medicine, Division of Endocrinology, Metabolism, Diabetes, University of Colorado, Aurora, CO, USA.
Anthony J GillSydney Medical School, University of Sydney, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0002-9447-1967
Arthur S TischlerTufts Medical Center, Boston, MA, USA.
Thomas GiordanoUniversity of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0003-0641-8873
Tamara ProdanovEunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA.
Jane R NobleChildren's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, Australia.
Roger R ReddelChildren's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, Australia.ORCID http://orcid.org/0000-0002-6302-6107
Alison H TrainerPeter MacCallum Cancer Centre, Melbourne, Australia.
Hans Kumar GhayeeUniversity of Florida and Malcom Randall VA Medical Center, Gainesville, FL, USA.
Isabelle BourdeauDivision of endocrinology and Research Center, Center hospitalier de l'Université de Montréal, Montreal, Canada.
Marianne ElstonWaikato Clinical Campus, University of Auckland, Hamilton, New Zealand.ORCID http://orcid.org/0000-0002-0748-2300
Diana IshakCancer Genetics Service, National Cancer Center Singapore, Singapore, Singapore.
Joanne Ngeow Yuen YieCancer Genetics Service, National Cancer Center Singapore, Singapore, Singapore.
Rodney J HicksSt Vincent's Dept of Medicine, University of Melbourne, Melbourne, VIC, Australia.ORCID http://orcid.org/0000-0002-0758-0824
Joakim CronaDepartment of Medical Sciences, Uppsala University, Uppsala, Sweden.ORCID http://orcid.org/0000-0003-0677-4894
Tobias ÅkerströmDepartment of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Peter StålbergDepartment of Surgical Sciences, Uppsala University, Uppsala, Sweden.ORCID http://orcid.org/0000-0002-9625-1394
Patricia DahiaDiv. Hematology and Medical Oncology, Department of Medicine, Mays Cancer Center, University of Texas Health Science Center at San Antonio (UTHSCSA), San Antonio, TX, USA.ORCID http://orcid.org/0000-0002-7757-370X
Sean GrimmondCentre for Cancer Research and Department of Clinical Pathology, University of Melbourne, VIC, Australia.ORCID http://orcid.org/0000-0002-8102-7998
Roderick Clifton-Bligh *Kolling Institute of Medical Research, Royal North Shore Hospital St Leonards NSW, Melbourne, Australia. roderick.cliftonbligh@sydney.edu.au.ORCID http://orcid.org/0000-0002-1545-0368
Karel Pacak *Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA. karel@mail.nih.gov.ORCID http://orcid.org/0000-0002-3541-3767
Richard W Tothill *Centre for Cancer Research and Department of Clinical Pathology, University of Melbourne, VIC, Australia. rtothill@unimelb.edu.au.ORCID http://orcid.org/0000-0003-4522-1184

Funding

Evaluating the impact of genetic ancestry on the biology and drug response profile of pheochromocytoma and paraganglioma-derived organoid modelsR01CA264248 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI DAHIA, PATRICIA LEAL, SORAGNI, ALICE · 2021 to 2025
$3.2M
Inherited genetic variation and penetrance of Hereditary Paraganglioma-Pheochromocytoma SyndromeR01CA246586 · NCI · UNIVERSITY OF COLORADO DENVER · PI FISHBEIN, LAUREN MICHELLE · 2020 to 2024
$1.8M
Interaction of the TMEM127 tumor suppressor with the mTORC1 lysosomal activating complexR01GM114102 · NIGMS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI DAHIA, PATRICIA LEAL · 2017 to 2021
$1.5M
Department of Health | National Health and Medical Research Council (NHMRC) APP1108032NCI NIH HHS R01 CA246586NCI NIH HHS R01 CA264248NIGMS NIH HHS R01 GM114102U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) GM114102U.S. Department of Health & Human Services | NIH | NCI | Division of Cancer Epidemiology and Genetics, National Cancer Institute (National Cancer Institute Division of Cancer Epidemiology and Genetics) CA264248Victorian Cancer Agency (VCA) TP828750
6 · The paper itself

Abstract

Hereditary SDHB-mutant pheochromocytomas (PC) and paragangliomas (PG) are rare tumours with a high propensity to metastasize although their clinical behaviour is unpredictable. To characterize the genomic landscape of these tumours and identify metastasis biomarkers, we perform multi-omic analysis on 94 tumours from 79 patients using seven molecular methods. Sympathetic (chromaffin cell) and parasympathetic (non-chromaffin cell) PCPG have distinct molecular profiles reflecting their cell-of-origin and biochemical profile. TERT and ATRX-alterations are associated with metastatic PCPG and these tumours have an increased mutation load, and distinct transcriptional and telomeric features. Most PCPG have quiet genomes with some rare co-operative driver events, including EPAS1/HIF-2α mutations. Two mechanisms of acquired resistance to DNA alkylating chemotherapies are identifiable; MGMT overexpression and mismatch repair-deficiency causing hypermutation. Our comprehensive multi-omic analysis of SDHB-mutant PCPG therefore identifies features of metastatic disease and treatment response, expanding our understanding of these rare neuroendocrine tumours.

Indexed as

Adrenal Gland NeoplasmsParagangliomaPheochromocytomaSuccinate DehydrogenaseAdultAgedBasic Helix-Loop-Helix ProteinsBiomarkers, TumorDNA Modification MethylasesDNA Repair EnzymesEndothelial PAS Domain-Containing Protein 1FemaleHumansMaleMiddle AgedMultiomicsATRX protein, humanBasic Helix-Loop-Helix ProteinsBiomarkers, TumorDNA Modification MethylasesDNA Repair EnzymesEndothelial PAS Domain-Containing Protein 1MGMT protein, humanSDHB protein, humanSuccinate DehydrogenaseTelomeraseTERT protein, humanTumor Suppressor ProteinsX-linked Nuclear Protein

Identifiers

PMID40097403
PMCPMC11914184

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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.