Responses to Crizotinib Can Occur in High-Level MET-Amplified Non-Small Cell Lung Cancer Independent of MET Exon 14 Alterations.
Activation of the MET proto-oncogene (MET) highly sensitive to MET inhibition has recently been described in NSCLC through two mechanisms: high-level amplification of the MNNG HOS Transforming gene (MET) (usually expressed relative to the chromosome 7 centromere [CEP7] when using fluorescence in situ hybridization) and exon 14 alterations. As partial overlap of these biomarkers occurs, whether one is purely a surrogate for the other or both can represent true oncogenic driver states continues to be explored. Cases of MET inhibitor-sensitive NSCLC harboring exon 14 alterations without coincident amplification have already been described. Here we report two cases of MET inhibitor-sensitive NSCLC harboring high-level MET amplification (MET/CEP7 ratio ≥5) without coincident exon 14 alterations, suggesting that these two methods of MET activation can produce independent MET-addicted states in NSCLC. Molecular profiling designed to capture all cases of potentially MET-addicted NSCLC should address both activation mechanisms.
Clinical Oncology, Cancer Institute of the State of São Paulo, School of Medicine, University of São Paulo, São Paulo, Brazil.
Rafael
R
Caparica
Clinical Oncology, Cancer Institute of the State of São Paulo, School of Medicine, University of São Paulo, São Paulo, Brazil; Sírio Libanês Hospital, São Paulo, Brazil.
Cheng Tzu
CT
Yen
Sírio Libanês Hospital, São Paulo, Brazil.
Renata
R
Coudry
Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Irvine, California.
Sai-Hong Ignatius
SI
Ou
Division of Medical Oncology, University of Colorado, Aurora, Colorado.
Marileila
M
Varella-Garcia
Division of Medical Oncology, University of Colorado, Aurora, Colorado. Electronic address: ross.camidge@ucdenver.edu.
D Ross
DR
Camidge
Clinical Oncology, Cancer Institute of the State of São Paulo, School of Medicine, University of São Paulo, São Paulo, Brazil; Sírio Libanês Hospital, São Paulo, Brazil.
Gilberto
G
de Castro
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000077547:Crizotinib; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005091:Exons / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D000090063:Proto-Oncogene Mas; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*; D011720:Pyrazoles / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*
D014408:Biomarkers, Tumor; C000715470:MAS1 protein, human; D047428:Protein Kinase Inhibitors; D000090063:Proto-Oncogene Mas; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
Crizotinib; Exon 14; Lung cancer; MET amplification