Somatic Mutations and Splicing Variants of Focal Adhesion Kinase in Non-Small Cell Lung Cancer.

摘要: Background Overexpression of focal adhesion kinase (FAK) has been reported in lung cancer, but the somatic mutations and alternative splicing variants this nonreceptor tyrosine remain to be investigated. Methods FAK 91 cancer patients was sequenced using genomic DNA cDNA samples tumor paired normal tissues as templates, RNA-seq data The Cancer Genome Atlas (TCGA) set were assessed. biological functions abnormal transcripts their response inhibitors analyzed eight cell lines activity assay, trypan blue exclusion MTT (3-(4, 5)-dimethylthiahiazo (-z-y1)-3, 5-di-phenytetrazoliumromide) transwell assay. Results We identified an internal tandem duplication (ITD), A1004S point mutation, exon 5-27 deletion (ΔE5-27) truncation variant, four FAK6,7 (containing exons for Boxes 6 7) seven (7.7%) patients. Smokers had more abnormalities than nonsmokers. In FAK-ITD, sequence encoding C-terminal FERM domain duplicated in-frame produced a protein product with elevated autophosphorylation sensitivity inhibitors. detected not counterpart (4.4%) TCGA data, Box and/or 7 (Box 6/7)-containing positive 42 (8.3%) 508 adenocarcinomas (LUADs) 37 (7.4%) 501 squamous carcinomas, smokers higher expression 6/7 (+) reformed or nonsmokers LUAD. promoted proliferation migration, exhibited increased autophosphorylation, sensitive inhibitor compared wild-type FAK. Conclusions Somatic may have role carcinogenesis represent potential biomarkers FAK-targeted therapies.