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MET Exon 14 Skipping in Non-Small Cell Lung Cancer.

Authors
 REBECCA S. HEIST  ;  HYO SUP SHIM  ;  SHALINI GINGIPALLY  ;  MARI MINO-KENUDSON  ;  LONG LE  ;  JUSTIN F. GAINOR  ;  ZONGLI ZHENG  ;  MARTIN ARYEE  ;  JUNFENG XIA  ;  PEILIN JIA,  ;  HAILING JIN  ;  ZHONGMING ZHAO  ;  WILLIAM PAO  ;  JEFFREY A. ENGELMAN  ;  A. JOHN IAFRATE 
Citation
 ONCOLOGIST, Vol.21(4) : 481-486, 2016 
Journal Title
 ONCOLOGIST 
ISSN
 1083-7159 
Issue Date
2016
MeSH
Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung/genetics* ; Carcinoma, Non-Small-Cell Lung/pathology ; Carcinoma, Non-Small-Cell Lung/therapy* ; Exons/genetics ; Female ; Gene Rearrangement/genetics ; Humans ; Male ; Middle Aged ; Molecular Targeted Therapy ; Neoplasm Recurrence, Local/genetics* ; Neoplasm Recurrence, Local/pathology ; Neoplasm Staging ; Proto-Oncogene Proteins c-met/antagonists & inhibitors ; Proto-Oncogene Proteins c-met/genetics* ; Smoking/adverse effects
Keywords
Lung cancer ; MET exon 14 skipping ; Targeted therapy
Abstract
BACKGROUND: Non-small cell lung cancers (NSCLCs) harboring specific genetic alterations can be highly sensitive to targeted therapies. MATERIALS AND METHODS: We performed a targeted rearrangement assay on 54 NSCLCs across all stages that were from patients who were never smokers and did not have driver mutations. Because MET exon 14 skipping was the most frequent alteration found, we surveyed the results for MET exon 14 skipping at Massachusetts General Hospital (MGH) since the inclusion of this alteration into our current molecular profiling panel. RESULTS: In a cohort of 54 never-smokers with lung cancers that were wild-type for known driver mutations, MET exon 14 skipping was the most frequently recurring alteration, occurring in 10 cancers (19%). Clinical testing at MGH via our next-generation sequencing (NGS) and NGS-rearrangement panels showed an additional 16 cases of MET exon 14 skipping, for an overall estimated frequency of 5.6%. A clinical case of a patient with MET exon 14 skipping treated with the MET inhibitor crizotinib is also described. CONCLUSION: MET exon 14 skipping is a targetable gene alteration found in NSCLC. Patients with these alterations may respond well to MET inhibition. IMPLICATIONS FOR PRACTICE: MET exon 14 skipping occurs with an approximately 5% frequency in NSCLC and is seen in both squamous and adenocarcinoma histology. Patients whose cancers have MET exon 14 skipping can respond well to MET inhibitors. Molecular testing for MET exon 14 skipping should be performed on all lung cancers because this is a targetable alteration.
Full Text
http://theoncologist.alphamedpress.org/content/21/4/481.abstract
DOI
10.1634/theoncologist.2015-0510
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Shim, Hyo Sup(심효섭) ORCID logo https://orcid.org/0000-0002-5718-3624
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/147128
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