Evidence map›Paper›PMID 40373350›Full record

ArticleESMO open2025

Performance and considerations in the use of diagnostic mutation panels for clonality testing in non-small-cell lung carcinoma.

J Janssen, B Andrade Barbosa, J C Machado, P Hofman, Y Kim, B Ylstra, T Radonic

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Article in ESMO open, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
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1 · What the graph read from it

What it found

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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

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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

2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

J JanssenDepartment of Pathology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
B Andrade BarbosaDepartment of Pathology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
J C MachadoInstitute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, France; Institute for Research and Innovation in Health (i3S), Porto, Portugal; Faculty of Medicine of the University of Porto, Porto, Portugal.
P HofmanClinical and Molecular Pathology Department, IHU RespirERA, Nice, France.
Y KimDepartment of Pathology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
B YlstraDepartment of Pathology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, France; Institute for Research and Innovation in Health (i3S), Porto, Portugal.
T RadonicDepartment of Pathology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. Electronic address: t.radonic@amsterdamumc.nl.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionNext-generation sequencing (NGS) mutation panels are widely implemented and commonly applied to aid clonality classification for non-small-cell lung carcinoma (NSCLC) patients with multiple tumors. Performance of different NGS panels for clonality classification, however, remains unresolved.

methodsWe assembled 210 primary and metastatic pairs from lung adenocarcinoma (LUAD) and lung squamous-cell carcinomas (LUSC) of the TRACERx421 cohort for which gold standard clonality was confirmed by whole exome sequencing. We used four NGS panels ranging from 12 to 523 genes to determine clonality using the 2024 International Association for the Study of Lung Cancer (IASLC) recommendations.

resultsWith an oncogene panel, 30% LUAD and 74% LUSC pairs remained inconclusive with, respectively, 2% and 0% misclassified. Addition of tumor suppressor genes results in 5% LUAD and 5% LUSC inconclusive and, respectively, 2% and 1% misclassified. For large panels, 0%-1% was inconclusive and 1% misclassified for both LUAD and LUSC. Misclassifications occurred due to discordant KRAS mutations in clonal pairs or coincidentally shared PIK3CA mutations in non-clonal pairs.

conclusionOncogene panels result in many inconclusive results, most of which can be resolved by adding tumor suppressor genes. Notwithstanding, 1%-2% of patients remain challenging. Large NGS panels detect mutations in more genes than the IASLC recommendations, allowing definitive clonality classification.

Indexed as

Carcinoma, Non-Small-Cell LungLung NeoplasmsMutationAgedFemaleHigh-Throughput Nucleotide SequencingHumansMaleMiddle Ageddiagnostic test accuracy (DTA)multiple pulmonary tumorsnext-generation sequencing (NGS)whole exome sequencing (WES)

Identifiers

PMID40373350
PMCPMC12141053

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