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MET Amplification Status in Therapy-Naïve Adeno- and Squamous Cell Carcinomas of the Lung

Overview of attention for article published in Clinical Cancer Research, February 2015
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Title
MET Amplification Status in Therapy-Naïve Adeno- and Squamous Cell Carcinomas of the Lung
Published in
Clinical Cancer Research, February 2015
DOI 10.1158/1078-0432.ccr-14-0450
Pubmed ID
Authors

Hans-Ulrich Schildhaus, Anne M. Schultheis, Josef Rüschoff, Elke Binot, Sabine Merkelbach-Bruse, Jana Fassunke, Wolfgang Schulte, Yon-Dschun Ko, Andreas Schlesinger, Marc Bos, Masyar Gardizi, Walburga Engel-Riedel, Michael Brockmann, Monika Serke, Ulrich Gerigk, Khosro Hekmat, Konrad F. Frank, Marcel Reiser, Holger Schulz, Stefan Krüger, Erich Stoelben, Thomas Zander, Jürgen Wolf, Reinhard Buettner

Abstract

Purpose: MET is a potential therapeutic target in lung cancer and both MET tyrosine kinase inhibitors and monoclonal antibodies have entered clinical trials. MET signaling can be activated by various mechanisms including gene amplification. In this study we aimed to investigate MET amplification status in adeno- and squamous cell carcinomas of the lung. We propose clearly defined amplification scores and provide epidemiologic data on MET amplification in lung cancer. Experimental design: We evaluated the prevalence of increased MET gene copy numbers in 693 treatment-naïve cancers by fluorescence in situ hybridization, defined clear cut-off criteria, and correlated FISH results to MET immunohistochemistry. Results: Two thirds (67%) of lung cancers do not have gains in MET gene copy numbers whereas 3% show a clear-cut high-level amplification (MET/centromer7 ratio ≥2.0 or average gene copy number per nucleus ≥6.0 or ≥10% of tumor cells containing ≥15 MET copies). The remaining cases can be subdivided into intermediate (6%) and low level gains (24%). Importantly, MET amplifications occur at equal frequencies in squamous and adenocarcinomas without or with EGFR or KRAS mutations. Conclusion: MET amplification is not a mutually exclusive genetic event in therapy-naïve NSCLC. Our data suggest that it might be useful to determine MET amplification a) before EGFR inhibitor treatment to identify possible primary resistance to anti-EGFR treatment, and b) to select cases that harbor KRAS mutations additionally to MET amplification and, thus, may not benefit from MET inhibition. Furthermore, our study provides comprehensive epidemiologic data for upcoming trials with various MET inhibitors.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 68 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
France 1 1%
Unknown 67 99%

Demographic breakdown

Readers by professional status Count As %
Researcher 15 22%
Other 9 13%
Student > Ph. D. Student 8 12%
Student > Master 7 10%
Student > Bachelor 5 7%
Other 9 13%
Unknown 15 22%
Readers by discipline Count As %
Medicine and Dentistry 22 32%
Biochemistry, Genetics and Molecular Biology 11 16%
Agricultural and Biological Sciences 6 9%
Pharmacology, Toxicology and Pharmaceutical Science 3 4%
Chemistry 2 3%
Other 6 9%
Unknown 18 26%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 22 February 2015.
All research outputs
#13,925,649
of 22,774,233 outputs
Outputs from Clinical Cancer Research
#9,679
of 12,585 outputs
Outputs of similar age
#131,202
of 257,413 outputs
Outputs of similar age from Clinical Cancer Research
#140
of 214 outputs
Altmetric has tracked 22,774,233 research outputs across all sources so far. This one is in the 37th percentile – i.e., 37% of other outputs scored the same or lower than it.
So far Altmetric has tracked 12,585 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.7. This one is in the 21st percentile – i.e., 21% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 257,413 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 47th percentile – i.e., 47% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 214 others from the same source and published within six weeks on either side of this one. This one is in the 31st percentile – i.e., 31% of its contemporaries scored the same or lower than it.