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Title
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The role of c-Met as a biomarker and player in innate and acquired resistance in non-small-cell lung cancer : two new mutations warrant further studies
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Author
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Abstract
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| The c-Met receptor is a therapeutically actionable target in non-small-cell lung cancer (NSCLC), with one approved drug and several agents in development. Most suitable biomarkers for patient selection include c-Met amplification and exon-14 skipping. Our retrospective study focused on the frequency of different c-Met aberrations (overexpression, amplification and mutations) in 153 primary, therapy-naive resection samples and their paired metastases, from Biobank@UZA. Furthermore, we determined the correlation of c-Met expression with clinicopathological factors, Epidermal Growth Factor Receptor (EGFR)-status and TP53 mutations. Our results showed that c-Met expression levels in primary tumors were comparable to their respective metastases. Five different mutations were detected by deep sequencing: three (E168D, S203T, N375S) previously described and two never reported (I333T, G783E). I333T, a new mutation in the Sema(phorin) domain of c-Met, might influence the binding of antibodies targeting the HGF-binding domain, potentially causing innate resistance. E168D and S203T mutations showed a trend towards a correlation with high c-Met expression (p = 0.058). We found a significant correlation between c-MET expression, EGFR expression (p = 0.010) and EGFR mutations (p = 0.013), as well as a trend (p = 0.057) with regards to TP53 mutant activity. In conclusion this study demonstrated a strong correlation between EGFR mutations, TP53 and c-Met expression in therapy-naive primary resection samples. Moreover, we found two new c-Met mutations that warrant further studies. |
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Language
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English
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Source (journal)
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Molecules: a journal of synthetic chemistry and natural product chemistry. - Bazel
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Publication
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Bazel
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2019
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ISSN
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1420-3049
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DOI
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10.3390/MOLECULES24244443
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Volume/pages
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24
:24
(2019)
, 15 p.
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Article Reference
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4443
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ISI
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000507299600021
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Pubmed ID
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31817278
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Medium
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E-only publicatie
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Full text (Publisher's DOI)
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Full text (open access)
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