Next-generation Sequencing for ALK and ROS1 Rearrangement Detection in Patients With Non-small-cell Lung Cancer: Implications of FISH-positive Patterns.
Adult
Aged
Aged, 80 and over
Anaplastic Lymphoma Kinase
/ genetics
Carcinoma, Non-Small-Cell Lung
/ diagnosis
Female
Gene Rearrangement
High-Throughput Nucleotide Sequencing
/ methods
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Lung Neoplasms
/ diagnosis
Male
Middle Aged
Protein-Tyrosine Kinases
/ genetics
Proto-Oncogene Proteins
/ genetics
Reproducibility of Results
Survival Analysis
Concurrent alterations
Fluorescence in situ hybridization
Gene copy number variations
Resistance mutations
Targeted therapies
Journal
Clinical lung cancer
ISSN: 1938-0690
Titre abrégé: Clin Lung Cancer
Pays: United States
ID NLM: 100893225
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
09
11
2018
revised:
13
02
2019
accepted:
17
02
2019
pubmed:
23
3
2019
medline:
4
4
2020
entrez:
23
3
2019
Statut:
ppublish
Résumé
Detection of ALK and ROS1 gene rearrangements in non-small-cell lung cancer is required for directing patient care. Although fluorescence in situ hybridization (FISH) and immunohistochemistry have been established as gold standard methods, next-generation sequencing (NGS) platforms are called to be at least equally successful. Comparison of these methods for translation into daily use is currently under investigation. Forty non-small-cell lung cancer paraffin-embedded samples with previous ALK (n = 33) and ROS1 (n = 7) FISH results were examined with the Oncomine Focus Assay and tested for ALK and ROS1 immunoreactivity. Clinical implications of concurrent molecular alterations and concordance between methods were evaluated. NGS was successful in 32 (80%) cases: 25 ALK and 7 ROS1. Few concomitant alterations were detected: 1 ALK rearranged case had an ALK p.L1196M-resistant mutation, 4 had CDK4, MYC, and/or ALK amplifications, and 1 ROS1 rearranged case showed a FGFR4 amplification. Comparison between techniques revealed 5 (16%) discordant cases that had lower progression-free survival than concordant cases: 7.6 (95% confidence interval, 2.2-13) versus 19.4 (95% confidence interval, 10.1-28.6). Remarkably, 4 of these cases had isolated 3' signal FISH pattern (P = .026). Our data support that the identification of 3' isolated signal FISH pattern in ALK and ROS1 cases might suggest a false-positive result. NGS seems a reliable technique to assess ALK and ROS1 rearrangements, offering the advantage over immunohistochemistry of detecting other molecular alterations with potential therapeutic implications.
Sections du résumé
BACKGROUND
Detection of ALK and ROS1 gene rearrangements in non-small-cell lung cancer is required for directing patient care. Although fluorescence in situ hybridization (FISH) and immunohistochemistry have been established as gold standard methods, next-generation sequencing (NGS) platforms are called to be at least equally successful. Comparison of these methods for translation into daily use is currently under investigation.
PATIENTS AND METHODS
Forty non-small-cell lung cancer paraffin-embedded samples with previous ALK (n = 33) and ROS1 (n = 7) FISH results were examined with the Oncomine Focus Assay and tested for ALK and ROS1 immunoreactivity. Clinical implications of concurrent molecular alterations and concordance between methods were evaluated.
RESULTS
NGS was successful in 32 (80%) cases: 25 ALK and 7 ROS1. Few concomitant alterations were detected: 1 ALK rearranged case had an ALK p.L1196M-resistant mutation, 4 had CDK4, MYC, and/or ALK amplifications, and 1 ROS1 rearranged case showed a FGFR4 amplification. Comparison between techniques revealed 5 (16%) discordant cases that had lower progression-free survival than concordant cases: 7.6 (95% confidence interval, 2.2-13) versus 19.4 (95% confidence interval, 10.1-28.6). Remarkably, 4 of these cases had isolated 3' signal FISH pattern (P = .026).
CONCLUSION
Our data support that the identification of 3' isolated signal FISH pattern in ALK and ROS1 cases might suggest a false-positive result. NGS seems a reliable technique to assess ALK and ROS1 rearrangements, offering the advantage over immunohistochemistry of detecting other molecular alterations with potential therapeutic implications.
Identifiants
pubmed: 30898567
pii: S1525-7304(19)30058-0
doi: 10.1016/j.cllc.2019.02.008
pii:
doi:
Substances chimiques
Proto-Oncogene Proteins
0
ALK protein, human
EC 2.7.10.1
Anaplastic Lymphoma Kinase
EC 2.7.10.1
Protein-Tyrosine Kinases
EC 2.7.10.1
ROS1 protein, human
EC 2.7.10.1
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e421-e429Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.