Abstract 5022
Background
MET amplifications present a potential therapeutic target in NSCLC and while FISH is conventionally used to asses it, there is no clinically defined cutoff. NGS is becoming routine in molecular diagnostics, and provides a means to assess MET amplification in the context of comprehensive genomic profiling. Here, we assess MET amplifications in NSCLC, in addition to TMB and concomitant driver mutations.
Methods
222 NSCLC cases were screened, and 26 samples were selected based on increased MET gene copy number (GCN) detected by FISH (Cappuzzo score, MET GCN >5). Cases were reclassified to determine amplification versus high polysomy by University of Colorado Cancer Center (UCCC) FISH-criteria. Archival tissue samples were evaluated by PGDx elio™ tissue complete (assay under development; Personal Genome Diagnostics), a 500+ gene NGS panel.
Results
Eight patients were amplified by UCCC FISH-criteria (1 patient high-amplified (MET/CEP7 >5) and 7 patients intermediate-amplified (>2.2 to < 5)). Five of these 8 patients (4 intermediate-amplified; 1 high-amplified) were also found to have MET amplification by NGS (>3 fold cutoff) and were male smokers, with a median age of 57 years, with no concurrent driver alterations. One MET-amplified sample also had a concomitant exon 14 skipping mutation. The 3 discordant cases were highly heterogeneous by FISH with focal MET amplifications. Eighteen patients exhibited high copy number gain by FISH but were negative for MET amplifications according to UCCC FISH-criteria and NGS. Five of these cases had driver mutations (2 = KRAS exon 2 mutations and 3 = EGFR sensitizing mutations). TMB scores in NGS MET-positive were lower than NGS MET-negative cases: 5.9 vs. 12.5 mut/Mb exome equivalent.
Conclusions
NGS and FISH produced similar MET amplification status. The wide range of MET classifications via FISH, together with tumor heterogeneity and lack of clinically relevant thresholds, could contribute to discordance. In most cases negative for MET amplification by NGS, alternative driver mutations and/or higher TMB were identified. These results suggest that, while these technologies provide complementary value, further clinical data is needed to define clinically meaningful MET alterations.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
E. Weingartner: Full / Part-time employment: Personal Genome Diagnostics. G. Cerqueira: Full / Part-time employment: Personal Genome Diagnostics. D. Nichol: Full / Part-time employment: Personal Genome Diagnostics. J. Simmons: Full / Part-time employment: Personal Genome Diagnostics. All other authors have declared no conflicts of interest.
Resources from the same session
5255 - [18F]-FDG PET/CT in predicting PD-L1 status in nasopharyngeal carcinoma
Presenter: Liang Zhao
Session: Poster Display session 1
Resources:
Abstract
4910 - Expression of PD-L1 in Chinese Patients with Common Cancers
Presenter: Min Zheng
Session: Poster Display session 1
Resources:
Abstract
4227 - The clearance of EGF by tumor-associated macrophages is suppressed by chemotherapeutic agent cisplatin
Presenter: Irina Larionova
Session: Poster Display session 1
Resources:
Abstract
5222 - VHIO-300 and a thousand one nights, a tale of Precision Medicine
Presenter: Ginevra Caratù
Session: Poster Display session 1
Resources:
Abstract
5668 - Matched Whole-Genome Sequencing and Whole-Exome Sequencing with Circulating Tumor DNA (ctDNA) Analysis are complementary modalities in clinical practice
Presenter: Robin Imperial
Session: Poster Display session 1
Resources:
Abstract
5772 - Exploring the role of genes associated with familial cancer syndromes on the development of multiple primary tumors
Presenter: Atanaska Mitkova
Session: Poster Display session 1
Resources:
Abstract
4784 - Doxorubicin resistance: early and advanced tumors can use two different strategies based on initial and profound abnormalities in microRNA expression signature
Presenter: Volodymyr Halytskiy
Session: Poster Display session 1
Resources:
Abstract
3456 - From tumor transcriptomes to underlying cell type proportions to better predict prognosis and response to treatments
Presenter: Yuna Blum
Session: Poster Display session 1
Resources:
Abstract
4976 - Optimization of automated germline DNA extraction from non-tumoral formalin-fixed paraffin embedded (FFPE) tissues
Presenter: Omar Youssef
Session: Poster Display session 1
Resources:
Abstract
4242 - HIV, HBV and HCV screening practices in oncology: a cross-sectional interregional survey
Presenter: Isabelle Poizot-Martin
Session: Poster Display session 1
Resources:
Abstract