Identification of MET exon14 skipping by targeted DNA- and RNA-based next-generation sequencing in pulmonary sarcomatoid carcinomas

Lung Cancer : Journal of the International Association for the Study of Lung Cancer
Yan LiJianming Ying

Abstract

Pulmonary sarcomatoid carcinomas (PSCs) constitutes a heterogeneous group of NSCLCs, which show poor prognosis even with aggressive surgical treatment and postoperative chemotherapy. The detection MET exon14 skipping (METex14 skipping) in PSCs suggests the targeted therapeutic opportunities with MET TKIs. We detected MET exon14 alterations using both targeted DNA- and RNA-based Next Generation Sequencing (NGS) and elucidated the driver mutation profile of 77 Chinese PSC patients. We also collected and analyzed the demographic features and clinical outcomes of patients harboring METex14 skipping mutation. METex14 skipping was detected in 20.8% of PSCs. A concordance of 96.1% was observed for DNA- and RNA-based NGS. 13 different genomic variants were revealed to induce METex14 skipping, including indels (N = 1) at splice acceptor sites, base substitutions (N = 4) and indels (N = 5) at splice donor sites, indels (N = 2) in the ∼20bp intronic noncoding region adjacent to the splice acceptor site, and indels (N = 1) in the exonic region. Patients harboring METex14 skipping tended to be older than others. In most cases, METex14 skipping were exclusive to other tumor driver alterations, however, we detected one case with METex14 skipp...Continue Reading

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