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Genetic screening and molecular characterization of MET alterations in non-small cell lung cancer
Saigi, M; McLeer-Florin, A; Pros, E; Nadal, E; Brambilla, E; Sanchez-Cespedes, M.
Affiliation
  • Saigi, M; Bellvitge Biomedical Research Institute (IDIBELL). Genes and Cancer Group. Cancer Epigenetics and Biology Program (PEBC). Hospitalet de Llobregat. Spain
  • McLeer-Florin, A; Université Grenoble Alpes. Centre Hospitalier Universitaire Grenoble Alpes. Pôle de Biologie et Pathologie. Département d’Anatomie et Cytologie Pathologiques. Grenoble. France
  • Pros, E; Bellvitge Biomedical Research Institute (IDIBELL). Genes and Cancer Group. Cancer Epigenetics and Biology Program (PEBC). Hospitalet de Llobregat. Spain
  • Nadal, E; Bellvitge Biomedical Research Institute (IDIBELL). Department of Medical Oncology. Hospitalet de Llobregat. Spain
  • Brambilla, E; Université Grenoble Alpes. Centre Hospitalier Universitaire Grenoble Alpes. Pôle de Biologie et Pathologie. Département d’Anatomie et Cytologie Pathologiques. Grenoble. France
  • Sanchez-Cespedes, M; Bellvitge Biomedical Research Institute (IDIBELL). Genes and Cancer Group. Cancer Epigenetics and Biology Program (PEBC). Hospitalet de Llobregat. Spain
Clin. transl. oncol. (Print) ; 20(7): 881-888, jul. 2018. ilus, tab, graf
Article in English | IBECS | ID: ibc-173639
Responsible library: ES1.1
Localization: BNCS
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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Collection: National databases / Spain Health context: SDG3 - Health and Well-Being Health problem: Target 3.4: Reduce premature mortality due to noncommunicable diseases Database: IBECS Main subject: Carcinoma, Non-Small-Cell Lung / Proto-Oncogene Proteins c-met / Lung Neoplasms Type of study: Diagnostic study / Prognostic study / Screening study Limits: Adult / Aged / Female / Humans / Male Language: English Journal: Clin. transl. oncol. (Print) Year: 2018 Document type: Article Institution/Affiliation country: Bellvitge Biomedical Research Institute (IDIBELL)/Spain / Université Grenoble Alpes/France
Search on Google
Collection: National databases / Spain Health context: SDG3 - Health and Well-Being Health problem: Target 3.4: Reduce premature mortality due to noncommunicable diseases Database: IBECS Main subject: Carcinoma, Non-Small-Cell Lung / Proto-Oncogene Proteins c-met / Lung Neoplasms Type of study: Diagnostic study / Prognostic study / Screening study Limits: Adult / Aged / Female / Humans / Male Language: English Journal: Clin. transl. oncol. (Print) Year: 2018 Document type: Article Institution/Affiliation country: Bellvitge Biomedical Research Institute (IDIBELL)/Spain / Université Grenoble Alpes/France
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