Evidence map›Paper›PMID 42635851›Full record

ArticleEndocrine pathology2026

Comprehensive Genomic Analysis in Hereditary Adrenal and Extra-Adrenal Paragangliomas.

Helia Purnaghshband, Elif Tuzlali, Kamalika Bhandari Deka, Jeffrey P Bruce, Kirsten M Farncombe, Brittany Gillies, Stephenie D Prokopec, Trevor Pugh, Sarah Redmond, Laura Redondo and 4 more

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In one paragraph

Article in Endocrine pathology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

14 authors.

Helia PurnaghshbandPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID http://orcid.org/0000-0002-7731-1670
Elif TuzlaliOntario Institute for Cancer Research, Toronto, ON, Canada.
Kamalika Bhandari DekaPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Jeffrey P BrucePrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Kirsten M FarncombePrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID http://orcid.org/0000-0001-9413-201X
Brittany GilliesPrincess Margaret Cancer Centre, Bhalwani Familial Cancer Clinic, University Health Network, Toronto, ON, M5G 2C1, Canada.ORCID http://orcid.org/0000-0003-1389-8027
Stephenie D ProkopecPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Trevor PughPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID http://orcid.org/0000-0002-8073-5888
Sarah RedmondPrincess Margaret Cancer Centre, Bhalwani Familial Cancer Clinic, University Health Network, Toronto, ON, M5G 2C1, Canada.
Laura RedondoPrincess Margaret Cancer Centre, Bhalwani Familial Cancer Clinic, University Health Network, Toronto, ON, M5G 2C1, Canada.ORCID http://orcid.org/0009-0008-3528-6973
Hong WangGenetics Program, North York General Hospital, Toronto, ON, Canada.
Shereen EzzatPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Ozgur MeteDepartment of Pathology, University Health Network, Toronto, ON, Canada.ORCID http://orcid.org/0000-0003-0469-2801
Raymond H KimOntario Institute for Cancer Research, Toronto, ON, Canada. Raymond.kim@uhn.ca.ORCID http://orcid.org/0000-0002-2147-8674

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Adrenal and extra-adrenal paragangliomas (PPGLs) are highly heritable non-epithelial neuroendocrine neoplasms. Through a retrospective chart review of 110 individuals diagnosed with PPGLs at the University Health Network in Toronto, Canada (2011-2023), we characterized germline findings, tumor features, self-reported ethnicity, and variant reclassification across a multi-ethnic cohort using targeted germline panel sequencing, whole genome sequencing (WGS), and optical genome mapping (OGM). Panel sequencing identified pathogenic or likely pathogenic (P/LP) germline variants in 28.18% (31/110) of individuals, with five variants of uncertain significance (VUS) in PPGL predisposition genes reclassified to P/LP during the study period (32.7%, 36/110). VUS rates were comparable across ethnic groups (16.28%, 7/43 in the group of non-European ethnicities; 17.24%, 10/58 in the group of European ethnicities), but the non-European group had a lower rate of VUS-to-P/LP reclassification (28.57%, 2/7 vs. 40.0%, 4/10). Uninformative targeted panel testing was supplemented by WGS in seven individuals with succinate dehydrogenase (SDH)-deficient tumors, leading to detection of P/LP in 6/7 cases (85.7%). Broader sequencing also uncovered incidental P/LP variants in genes without an established PPGL association, including TSC1 and PALB2. OGM resolved a complex structural variant (SV) involving SDHA as an inverted tandem duplication that WGS alone could not fully characterize. Our findings support a tiered diagnostic approach: comprehensive germline panels and tumor SDHB immunohistochemistry to maximize solved cases, with WGS and OGM reserved for select unresolved cases, and highlight the importance of equitable variant interpretation across diverse PPGL populations.

Indexed as

Adrenal Gland NeoplasmsParaganglioma, Extra-AdrenalAdultAgedFemaleGenetic Predisposition to DiseaseGenomicsGerm-Line MutationHumansMaleMiddle AgedRetrospective StudiesWhole Genome SequencingHereditary paragangliomaMulti-ethnic populationOptical genome mappingSDHB protein immunohistochemistryWhole genome sequencing

Identifiers

PMID42635851
PMCPMC13503469

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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.