Multigene PCR using both cfDNA and cfRNA in the supernatant of pleural effusion achieves accurate and rapid detection of mutations and fusions of driver genes in patients with advanced NSCLC.
Anaplastic Lymphoma Kinase
/ genetics
Carcinoma, Non-Small-Cell Lung
/ genetics
Cell-Free Nucleic Acids
/ genetics
DNA, Neoplasm
Female
Gene Fusion
Genes, erbB-1
Genes, erbB-2
Genes, ras
Humans
Lung Neoplasms
/ genetics
Male
Middle Aged
Mutation
Pleural Effusion, Malignant
/ genetics
Polymerase Chain Reaction
/ methods
Sensitivity and Specificity
ALK fusion
NSCLC
PCR
cfRNA
pleural effusion
supernatant
Journal
Cancer medicine
ISSN: 2045-7634
Titre abrégé: Cancer Med
Pays: United States
ID NLM: 101595310
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
revised:
16
01
2021
received:
26
10
2020
accepted:
21
01
2021
pubmed:
4
3
2021
medline:
20
7
2021
entrez:
3
3
2021
Statut:
ppublish
Résumé
Pleural effusion from patients with advanced non-small cell lung cancer (NSCLC) has been proved valuable for molecular analysis, especially when the tissue sample not available. However, simultaneous detection of multiple driver gene alterations especially the fusions is still challenging. In this study, 77 patients with advanced NSCLC and pleural effusion were enrolled, 49 of whom had matched tumor tissues. Supernatants, cell sediments, and cell blocks were prepared from pleural effusion samples for detection of driver alterations by a PCR-based 9-gene mutation detection kit. Mutations in EGFR, KRAS, and HER2 were detected in DNA and cfDNA, fusions in ALK was detected in RNA and cfRNA. Compared with matched tumor tissue, the supernatant showed the highest overall sensitivity (81.3%), with 81.5% for SNV/Indels by cfDNA and 80% for fusions by cfRNA, followed by cell blocks (71.0%) and the cell sediments (66.7%). Within the group of treatment-naïve patients or malignant cells observed in the cell sediments, supernatant showed higher overall sensitivity (89.5% and 92.3%) with both 100% for fusions. CfDNA and cfRNA derived from pleural effusion supernatant have been successfully tested with a PCR-based multigene detection kit. Pleural effusion supernatant seems a preferred material for detection of multigene alterations to guide treatment decision of advanced NSCLC.
Sections du résumé
BACKGROUND
Pleural effusion from patients with advanced non-small cell lung cancer (NSCLC) has been proved valuable for molecular analysis, especially when the tissue sample not available. However, simultaneous detection of multiple driver gene alterations especially the fusions is still challenging.
METHODS
In this study, 77 patients with advanced NSCLC and pleural effusion were enrolled, 49 of whom had matched tumor tissues. Supernatants, cell sediments, and cell blocks were prepared from pleural effusion samples for detection of driver alterations by a PCR-based 9-gene mutation detection kit.
RESULTS
Mutations in EGFR, KRAS, and HER2 were detected in DNA and cfDNA, fusions in ALK was detected in RNA and cfRNA. Compared with matched tumor tissue, the supernatant showed the highest overall sensitivity (81.3%), with 81.5% for SNV/Indels by cfDNA and 80% for fusions by cfRNA, followed by cell blocks (71.0%) and the cell sediments (66.7%). Within the group of treatment-naïve patients or malignant cells observed in the cell sediments, supernatant showed higher overall sensitivity (89.5% and 92.3%) with both 100% for fusions.
CONCLUSIONS
CfDNA and cfRNA derived from pleural effusion supernatant have been successfully tested with a PCR-based multigene detection kit. Pleural effusion supernatant seems a preferred material for detection of multigene alterations to guide treatment decision of advanced NSCLC.
Identifiants
pubmed: 33656807
doi: 10.1002/cam4.3769
pmc: PMC7982639
doi:
Substances chimiques
Cell-Free Nucleic Acids
0
DNA, Neoplasm
0
ALK protein, human
EC 2.7.10.1
Anaplastic Lymphoma Kinase
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2286-2292Informations de copyright
© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
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