title: MET Exon 14 Skipping in Non-Small Cell Lung Cancer.
abstract: BACKGROUND
  Non-small cell lung cancers (NSCLCs) harboring specific genetic alterations can be highly sensitive to targeted therapies.
  
  
  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.
  
  
  CONCLUSIONS
  MET exon 14 skipping is a targetable gene alteration found in NSCLC. Patients with these alterations may respond well to MET inhibition.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cancer Center, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA rheist@partners.org.
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Heist
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA Department of Pathology, College of Medicine, Yonsei University, Seoul, Republic of Korea.
authors.forename: Hyo Sup
authors.initials: HS
authors.lastname: Shim
authors.affiliation: Cancer Center, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Shalini
authors.initials: S
authors.lastname: Gingipally
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Mari
authors.initials: M
authors.lastname: Mino-Kenudson
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Long
authors.initials: L
authors.lastname: Le
authors.affiliation: Cancer Center, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Justin F
authors.initials: JF
authors.lastname: Gainor
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Zongli
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Aryee
authors.affiliation: Institute of Health Sciences, Anhui University, Hefei, Anhui, People's Republic of China Department of Biomedical Informatics, School of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Xia
authors.affiliation: Department of Biomedical Informatics, School of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Peilin
authors.initials: P
authors.lastname: Jia
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, School of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Hailing
authors.initials: H
authors.lastname: Jin
authors.affiliation: Department of Biomedical Informatics, School of Medicine, Vanderbilt University, Nashville, Tennessee, USA Center for Precision Health, School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, School of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: William
authors.initials: W
authors.lastname: Pao
authors.affiliation: Cancer Center, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Engelman
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: A John
authors.initials: AJ
authors.lastname: Iafrate
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D005091:Exons / Q000235:genetics; D005260:Female; D015321:Gene Rearrangement / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects
chemical_list: C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: Lung cancer; MET exon 14 skipping; Targeted therapy