Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster Display session 1

5022 - Identification of MET gene amplifications using next-generation sequencing in non-small cell lung cancer patients

Date

28 Sep 2019

Session

Poster Display session 1

Topics

Pathology/Molecular Biology

Tumour Site

Non-Small Cell Lung Cancer

Presenters

Sergi Clavé

Citation

Annals of Oncology (2019) 30 (suppl_5): v797-v815. 10.1093/annonc/mdz269

Authors

S. Clavé1, M. Salido1, P. Rocha2, M. Hardy-Werbin2, J. Gibert3, X. Riera1, E. Weingartner4, G. Cerqueira4, D. Nichol4, J. Simmons4, Á. Taus2, L. Pijuan1, B. Bellosillo1, E. Arriola2

Author affiliations

  • 1 Pathology Department, Hospital del Mar, 08003 - Barcelona/ES
  • 2 Medical Oncology Department, Hospital del Mar, 08003 - Barcelona/ES
  • 3 Cancer Research Program, Hospital del Mar Medical Research Institute, 08003 - Barcelona/ES
  • 4 Translational Research, Personal Genome Diagnostics, 21224 - Baltimore/US

Resources

Login to access the resources on OncologyPRO.

If you do not have an ESMO account, please create one for free.

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.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.