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Oncologist. 2016 Apr;21(4):481-6. doi: 10.1634/theoncologist.2015-0510. Epub 2016 Mar 28.

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

Author information

1
Cancer Center, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA rheist@partners.org.
2
Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA Department of Pathology, College of Medicine, Yonsei University, Seoul, Republic of Korea.
3
Cancer Center, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
4
Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA.
5
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.
6
Department of Biomedical Informatics, School of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
7
Division of Hematology-Oncology, Department of Medicine, School of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
8
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.

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.

KEYWORDS:

Lung cancer; MET exon 14 skipping; Targeted therapy

PMID:
27022036
PMCID:
PMC4828128
DOI:
10.1634/theoncologist.2015-0510
[Indexed for MEDLINE]
Free PMC Article

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