11P - Prognostic impact of MET mutations in exon 14 and copy number alterations in a series of NSCLC patients

Date 15 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session Poster lunch
Topics Thoracic Malignancies
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Presenter Sergi Clavé
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors S. Clavé1, A. Dalmases1, R. Longarón1, L. Pijuan1, D. Casadevall2, Á. Taus2, B. Espinet1, E. Arriola3, B. Bellosillo1, M. Salido1
  • 1Pathology Department, Hospital del Mar, 08003 - Barcelona/ES
  • 2Oncology Department, Hospital del Mar, 08003 - Barcelona/ES
  • 3Cancer Sciences Unit, Southampton General Hospital, SO16 6YD - Southampton/GB

Abstract

Background

Mutations in the exon 14 of the MET gene affecting RNA splice acceptor and donor sites, which lead to exon skipping, have been recently associated to responsiveness to crizotinib. Up to date, patient selection for Met inhibitors has been made according to MET amplification/high polysomy and/or protein overexpression. We have investigated the prevalence of MET exon 14 mutations and their correlation with gene copy number alterations (CNAs) in NSCLC patients.

Methods

We tested 132 lung adenocarcinomas and adenosquamous carcinoma samples for mutations in MET exon 14 by Sanger sequencing and for MET gene CNAs by FISH (Abbott Molecular). We collected clinical data together with EGFR and KRAS mutational status and ALK, ROS1 and RET rearrangements.

Results

MET alterations were found in 23 patients (17.5%): 3 exon 14 skipping mutations (2.3%), 8 gene amplifications (6.1%), and 12 high polysomy cases (9.1%). Among the 11 MET altered cases (3 mutated and 8 amplified): 8 patients were male, with a median age of 64.5 years (range: 46–91), current or former smokers (50 pack/years, range: 30–80), and all were diagnosed in an advanced stage disease (III and IV). None of the 3 mutated cases had concurrent MET CNAs. One MET mutated case presented also a KRAS p.G12C substitution while the other two were wild type for EGFR (exons 18 to 21) and KRAS (exon 2). Interestingly, patients with MET alterations have a shorter overall survival (p 

Conclusions

We have identified alterations of the MET gene (mutations in exon 14 and CNAs) in 8.4% of NSCLC patients. Our data support the usefulness of prospective screening of MET exon 14 mutations and gene amplifications due to their prognostic and predictive role. These mutations define a new subset of NSCLC patients that should be analyzed independently of the MET gene copy number status.

Clinical trial identification

Legal entity responsible for the study

Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain

Funding

Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain

Disclosure

All authors have declared no conflicts of interest.