Clinical Utility and Performance of an Ultrarapid Multiplex RNA-Based Assay for Detection of ALK, ROS1, RET, and NTRK1/2/3 Rearrangements and MET Exon 14 Skipping Alterations.
Anaplastic Lymphoma Kinase
/ genetics
Exons
/ genetics
Gene Rearrangement
Humans
In Situ Hybridization, Fluorescence
Lung Neoplasms
/ genetics
Protein-Tyrosine Kinases
/ genetics
Proto-Oncogene Proteins
/ genetics
Proto-Oncogene Proteins c-ret
/ genetics
RNA
Receptor Protein-Tyrosine Kinases
/ genetics
Journal
The Journal of molecular diagnostics : JMD
ISSN: 1943-7811
Titre abrégé: J Mol Diagn
Pays: United States
ID NLM: 100893612
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
received:
23
09
2021
revised:
14
01
2022
accepted:
03
03
2022
pubmed:
18
4
2022
medline:
15
6
2022
entrez:
17
4
2022
Statut:
ppublish
Résumé
Several kinase fusions are established targetable drivers in lung cancers. However, rapid and comprehensive detection remains challenging because of diverse partner genes and breakpoints. We assess the clinical utility and performance of a rapid microfluidic multiplex real-time PCR-based assay for simultaneous query of fusions involving ALK, ROS1, RET, and NTRK1/2/3, as well as MET exon 14 skipping, using a 3-hour automated process. Dual analytic strategies were utilized: fusion-specific amplification and 3' to 5' expression imbalance. One-hundred and forty-three independent, formalin-fixed, paraffin-embedded tumor samples (112 surgical specimens, 31 cytologic cell blocks) were analyzed: 133 with known kinase gene alterations and 10 negative samples based on clinically validated next-generation sequencing. Testing was successful in 142 (99%) cases. The assay demonstrated a sensitivity of 97% (28/29), 100% (31/31), 92% (22/24), 81% (22/27), and 100% (20/20) for ALK, RET, ROS1, and NTRK1/2/3 rearrangements and MET exon 14 skipping alterations, respectively, with 100% specificity for all. Concordant results were achieved in specimens aged up to 5 years, with >10% tumor, and inputs of at least 9 mm
Identifiants
pubmed: 35430374
pii: S1525-1578(22)00080-0
doi: 10.1016/j.jmoldx.2022.03.006
pmc: PMC9227998
pii:
doi:
Substances chimiques
Proto-Oncogene Proteins
0
RNA
63231-63-0
Anaplastic Lymphoma Kinase
EC 2.7.10.1
Protein-Tyrosine Kinases
EC 2.7.10.1
Proto-Oncogene Proteins c-ret
EC 2.7.10.1
RET protein, human
EC 2.7.10.1
ROS1 protein, human
EC 2.7.10.1
Receptor Protein-Tyrosine Kinases
EC 2.7.10.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
642-654Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
Copyright © 2022 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
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