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Clinical and Translational Oncology
Published in: Clinical and Translational Oncology 7/2018

01-07-2018 | Research Article

Genetic screening and molecular characterization of MET alterations in non-small cell lung cancer

Authors: M. Saigi, A. McLeer-Florin, E. Pros, E. Nadal, E. Brambilla, M. Sanchez-Cespedes

Published in: Clinical and Translational Oncology | Issue 7/2018

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Abstract

Purpose

Aberrant activation of MET as a result of exon 14-skipping (METex14) mutations or gene amplification is an oncogenic mechanism in non-small cell lung carcinoma (NSCLC) and a potential therapeutic target. The purpose of this study was to characterize MET alterations in a cohort of NSCLC patients treated with surgery.

Methods and patients

157 NSCLCs of various histopathologies, including pulmonary sarcomatoid carcinomas (PSC), were tested for MET alterations. METex14 mutations, MET copy number alterations and the levels of MET protein were determined by Sanger sequencing, fluorescence in situ hybridization and immunohistochemistry, respectively. Concurrent alterations of other important cancer genes and immunostaining of the downstream effector, phopho-S6, were also determined.

Results

METex14 mutations and MET amplification were detected in seven tumors. MET genetic alterations were found predominantly in the lung adenocarcinoma (ADC) and PSC histopathologies. High levels of MET protein were found in most MET-amplified tumors, but not in all METex14-mutated tumors. Strong phopho-S6 staining was observed in about half of the MET-activated tumors. One tumor with METex14 exhibited concurrent ERBB2 amplification.

Conclusions

MET activation, by either METex14 mutations or amplification, is characteristic of a subset of early stage NSCLCs and may coexist with ERBB2 amplification. This may have potential therapeutic implications. The presence of METex14 mutations was associated with low levels of MET protein, which may limit the use of total MET immunostaining as a marker for preselecting patients for MET-targeted therapies.
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Metadata
Title
Genetic screening and molecular characterization of MET alterations in non-small cell lung cancer
Authors
M. Saigi
A. McLeer-Florin
E. Pros
E. Nadal
E. Brambilla
M. Sanchez-Cespedes
Publication date
01-07-2018
Publisher
Springer International Publishing
Published in
Clinical and Translational Oncology / Issue 7/2018
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-017-1799-7

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