PMID- 34638507
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211016
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 13
IP  - 19
DP  - 2021 Oct 7
TI  - MET Amplification in Non-Small Cell Lung Cancer (NSCLC)-A Consecutive Evaluation 
      Using Next-Generation Sequencing (NGS) in a Real-World Setting.
LID - 10.3390/cancers13195023 [doi]
LID - 5023
AB  - In non-small cell lung cancer (NSCLC), approximately 1-3% of cases harbor an 
      increased gene copy number (GCN) of the MET gene. This alteration can be due to 
      de novo amplification of the MET gene or can represent a secondary resistance 
      mechanism in response to targeted therapies. To date, the gold standard method to 
      evaluate the GCN of MET is fluorescence in situ hybridization (FISH). However, 
      next-generation sequencing (NGS) is becoming more relevant to optimize therapy by 
      revealing the mutational profile of each NSCLC. Using evaluable n = 205 NSCLC 
      cases of a consecutive cohort, this study addressed the question of whether an 
      amplicon based NGS assay can completely replace the FISH method regarding the 
      classification of MET GCN status. Out of the 205 evaluable cases, only n = 9 
      cases (43.7%) of n = 16 high-level MET amplified cases assessed by FISH were 
      classified as amplified by NGS. Cases harboring a MET GCN > 10 showed the best 
      concordance when comparing FISH versus NGS (80%). This study confirms that an 
      amplicon-based NGS assessment of the MET GCN detects high-level MET amplified 
      cases harboring a MET GCN > 10 but fails to detect the various facets of MET gene 
      amplification in the context of a therapy-induced resistance mechanism.
FAU - Schubart, Christoph
AU  - Schubart C
AUID- ORCID: 0000-0003-0084-9330
AD  - Institute of Pathology, University Hospital Erlangen, 
      Friedrich-Alexander-Universitat Erlangen-Nurnberg (FAU), 91054 Erlangen, Germany.
AD  - Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), 91054 Erlangen, Germany.
FAU - Stohr, Robert
AU  - Stohr R
AD  - Institute of Pathology, University Hospital Erlangen, 
      Friedrich-Alexander-Universitat Erlangen-Nurnberg (FAU), 91054 Erlangen, Germany.
AD  - Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), 91054 Erlangen, Germany.
FAU - Togel, Lars
AU  - Togel L
AUID- ORCID: 0000-0003-0612-6440
AD  - Institute of Pathology, University Hospital Erlangen, 
      Friedrich-Alexander-Universitat Erlangen-Nurnberg (FAU), 91054 Erlangen, Germany.
AD  - Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), 91054 Erlangen, Germany.
FAU - Fuchs, Florian
AU  - Fuchs F
AD  - Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), 91054 Erlangen, Germany.
AD  - Department of Medicine 1, University Hospital Erlangen, 
      Friedrich-Alexander-Universitat Erlangen-Nurnberg (FAU), 91054 Erlangen, Germany.
FAU - Sirbu, Horia
AU  - Sirbu H
AD  - Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), 91054 Erlangen, Germany.
AD  - Department of Thoracic Surgery, University Hospital Erlangen, 
      Friedrich-Alexander-Universitat Erlangen-Nurnberg (FAU), 91054 Erlangen, Germany.
FAU - Seitz, Gerhard
AU  - Seitz G
AD  - Institute of Pathology, Neuropathology, Molecular Diagnostics and Cytology, 
      Klinikum Bamberg, Sozialstiftung Bamberg, 96049 Bamberg, Germany.
FAU - Seggewiss-Bernhardt, Ruth
AU  - Seggewiss-Bernhardt R
AD  - Department of Medicine 5, Klinikum Bamberg, Sozialstiftung Bamberg, 96049 
      Bamberg, Germany.
FAU - Leistner, Rumo
AU  - Leistner R
AD  - Department of Medicine 4, Klinikum Bamberg, Sozialstiftung Bamberg, 96049 
      Bamberg, Germany.
FAU - Sterlacci, William
AU  - Sterlacci W
AD  - Institute of Pathology, Friedrich-Alexander-Universitat Erlangen-Nurnberg (FAU), 
      Klinikum Bayreuth, 95445 Bayreuth, Germany.
FAU - Vieth, Michael
AU  - Vieth M
AD  - Institute of Pathology, Friedrich-Alexander-Universitat Erlangen-Nurnberg (FAU), 
      Klinikum Bayreuth, 95445 Bayreuth, Germany.
FAU - Seidl, Christoph
AU  - Seidl C
AD  - Diagnosticum, Pathology and Cytology, 95032 Hof, Germany.
AD  - Diagnosticum, Laboratory Medicine, Microbiology, Pathology, Human Genetics, 09221 
      Neukirchen, Germany.
FAU - Mugler, Michael
AU  - Mugler M
AD  - Diagnosticum, Pathology and Cytology, 95032 Hof, Germany.
AD  - Diagnosticum, Laboratory Medicine, Microbiology, Pathology, Human Genetics, 09221 
      Neukirchen, Germany.
FAU - Kapp, Markus
AU  - Kapp M
AD  - Department of Gastroenterology, Hepatology and Infectiology, Section Hematology & 
      Oncology, Sana Klinikum Hof, 95032 Hof, Germany.
FAU - Hohenforst-Schmidt, Wolfgang
AU  - Hohenforst-Schmidt W
AD  - Department of Cardiology, Sana Klinikum Hof, 95032 Hof, Germany.
FAU - Hartmann, Arndt
AU  - Hartmann A
AD  - Institute of Pathology, University Hospital Erlangen, 
      Friedrich-Alexander-Universitat Erlangen-Nurnberg (FAU), 91054 Erlangen, Germany.
AD  - Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), 91054 Erlangen, Germany.
FAU - Haller, Florian
AU  - Haller F
AD  - Institute of Pathology, University Hospital Erlangen, 
      Friedrich-Alexander-Universitat Erlangen-Nurnberg (FAU), 91054 Erlangen, Germany.
AD  - Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), 91054 Erlangen, Germany.
FAU - Erber, Ramona
AU  - Erber R
AUID- ORCID: 0000-0003-0315-1229
AD  - Institute of Pathology, University Hospital Erlangen, 
      Friedrich-Alexander-Universitat Erlangen-Nurnberg (FAU), 91054 Erlangen, Germany.
AD  - Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), 91054 Erlangen, Germany.
LA  - eng
PT  - Journal Article
DEP - 20211007
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC8508248
OTO - NOTNLM
OT  - MET
OT  - MET inhibitor
OT  - NSCLC
OT  - amplification
OT  - fluorescence in situ hybridization
OT  - next-generation sequencing
OT  - precision medicine
OT  - resistance mechanism
COIS- A.H. has received honoraria from BMS, MSD, Roche, AstraZeneca, Boehringer 
      Ingelheim, Abbvie, Jansen-Cilag, and Ipsen. R.E. has received honoraria from 
      Roche, Eisai, Pfizer, and Novartis and travel grants from BioNTech. The 
      institution of A.H. and R.E. conducts research for AstraZeneca, Roche, 
      Janssen-Cilag, NanoString Technologies, Biocartis, Zytomed Systems, Novartis, 
      Cepheid, and BioNTech. R.S.B. received honoraria from BMS, Roche, MSD, Novartis, 
      Celgene, Amgen and Ipsen. W.S. and M.V. conduct research/received honoraria 
      for/from Falk, Pentax, Lilly, Malesci, AstraZeneca, Olympus, Leica, Rohe, 
      Boerhinger-Ingelheim.
EDAT- 2021/10/14 06:00
MHDA- 2021/10/14 06:01
PMCR- 2021/10/07
CRDT- 2021/10/13 01:02
PHST- 2021/08/12 00:00 [received]
PHST- 2021/09/26 00:00 [revised]
PHST- 2021/09/27 00:00 [accepted]
PHST- 2021/10/13 01:02 [entrez]
PHST- 2021/10/14 06:00 [pubmed]
PHST- 2021/10/14 06:01 [medline]
PHST- 2021/10/07 00:00 [pmc-release]
AID - cancers13195023 [pii]
AID - cancers-13-05023 [pii]
AID - 10.3390/cancers13195023 [doi]
PST - epublish
SO  - Cancers (Basel). 2021 Oct 7;13(19):5023. doi: 10.3390/cancers13195023.