Comparison of solid tissue sequencing and liquid biopsy accuracy in identification of clinically relevant gene mutations and rearrangements in lung adenocarcinomas.
Adenocarcinoma of Lung
/ blood
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor
/ blood
Circulating Tumor DNA
/ blood
DNA Mutational Analysis
Female
Gene Rearrangement
Genetic Predisposition to Disease
High-Throughput Nucleotide Sequencing
Humans
Liquid Biopsy
Lung Neoplasms
/ blood
Male
Middle Aged
Mutation
Phenotype
Predictive Value of Tests
Reproducibility of Results
Retrospective Studies
Journal
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
ISSN: 1530-0285
Titre abrégé: Mod Pathol
Pays: United States
ID NLM: 8806605
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
received:
08
02
2021
accepted:
14
07
2021
revised:
13
07
2021
pubmed:
8
8
2021
medline:
22
3
2022
entrez:
7
8
2021
Statut:
ppublish
Résumé
Screening for therapeutic targets is standard of care in the management of advanced non-small cell lung cancer. However, most molecular assays utilize tumor tissue, which may not always be available. "Liquid biopsies" are plasma-based next generation sequencing (NGS) assays that use circulating tumor DNA to identify relevant targets. To compare the sensitivity, specificity, and accuracy of a plasma-based NGS assay to solid-tumor-based NGS we retrospectively analyzed sequencing results of 100 sequential patients with lung adenocarcinoma at our institution who had received concurrent testing with both a solid-tissue-based NGS assay and a commercially available plasma-based NGS assay. Patients represented both new diagnoses (79%) and disease progression on treatment (21%); the majority (83%) had stage IV disease. Tissue-NGS identified 74 clinically relevant mutations, including 52 therapeutic targets, a sensitivity of 94.8%, while plasma-NGS identified 41 clinically relevant mutations, a sensitivity of 52.6% (p < 0.001). Tissue-NGS showed significantly higher sensitivity and accuracy across multiple patient subgroups, both in newly diagnosed and treated patients, as well as in metastatic and nonmetastatic disease. Discrepant cases involved hotspot mutations and actionable fusions including those in EGFR, ALK, and NTRK1. In summary, tissue-NGS detects significantly more clinically relevant alterations and therapeutic targets compared to plasma-NGS, suggesting that tissue-NGS should be the preferred method for molecular testing of lung adenocarcinoma when tissue is available. Plasma-NGS can still play an important role when tissue testing is not possible. However, given its low sensitivity, a negative result should be confirmed with a tissue-based assay.
Identifiants
pubmed: 34362997
doi: 10.1038/s41379-021-00880-0
pii: S0893-3952(22)00377-5
doi:
Substances chimiques
Biomarkers, Tumor
0
Circulating Tumor DNA
0
Types de publication
Comparative Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2168-2174Informations de copyright
© 2021. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.
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