Utility of different methods for detection of LC molecular targets
| Gene/Alterations | Variant-specific PCR | Sequencing of relevant DNA fragments | FISH | IHC | DNA-based NGS | RNA-based NGS | Other methods |
|---|---|---|---|---|---|---|---|
| EGFR mutations in exons 18, 19 and 21 | + | ++ | − | − | +++ | +++ | Capillary gel electrophoresis is reliable for detection of exon 19 deletions and insertions |
| EGFR exon 20 insertions | + | ++ | − | − | +++ | +++ | Capillary gel electrophoresis is reliable for detection of exon 20 insertions |
| BRAF mutations | + | ++ | − | − | +++ | +++ | |
| KRAS mutations | + | ++ | − | − | +++ | +++ | |
| ERBB2 (HER2) exon 20 insertions | + | ++ | − | − | +++ | +++ | Capillary gel electrophoresis is reliable for detection of exon 20 insertions |
| MET exon 14 skipping mutations | + | − | − | − | + | +++ | Comparison of expression of mutated vs. wild-type allele |
| ALK fusions | + | − | ++ | + | + | +++ | PCR test for unbalanced 5’/3’-end expression |
| ROS1 fusions | + | − | ++ | −/+ | + | +++ | PCR test for unbalanced 5’/3’-end expression (?) |
| RET fusions | + | − | − | − | + | +++ | PCR test for unbalanced 5’/3’-end expression |
| NTRK1−3 fusions | + | − | ++ | + | + | +++ | PCR test for unbalanced 5’/3’-end expression |
| TMB | − | − | − | − | +++ | + (?) | |
| PD-L1 expression | − | − | − | + | − | − |
+++: highly reliable method; ++: method with some limitations; +: method with significant limitations; −: inappropriate method; (?): not enough evidence. The blank cells indicate that no methods other than the ones marked by “+” symbols have been sufficiently validated for the testing of this molecular marker. FISH: fluorescence in situ hybridization; IHC: immunohistochemistry; NGS: next-generation sequencing; TMB: tumor mutation burden
We are cordially thankful to Dr. Priscilla Amankwah for her invaluable help in improving this manuscript.
ENI: Conceptualization, Investigation, Writing—original draft, Writing—review & editing, Supervision. EVP: Investigation, Visualization, Writing—review & editing. SVO: Validation, Writing—review & editing. All authors read and approved the submitted version.
The authors declare that they have no conflicts of interest.
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This research has been supported by the Russian Science Foundation, grant number [23-45-10038]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
© The Author(s) 2024.