biostudies-literatureImielinski MNCI NIH HHS1582-6https://www.ebi.ac.uk/biostudies/studies/S-EPMC3973082biostudies-literatureUnknown124(4)Targeted cancer therapies often induce "outlier" responses in molecularly defined patient subsets. One patient with advanced-stage lung adenocarcinoma, who was treated with oral sorafenib, demonstrated a near-complete clinical and radiographic remission for 5 years. Whole-genome sequencing and RNA sequencing of primary tumor and normal samples from this patient identified a somatic mutation, ARAF S214C, present in the cancer genome and expressed at high levels. Additional mutations affecting this residue of ARAF and a nearby residue in the related kinase RAF1 were demonstrated across 1% of an independent cohort of lung adenocarcinoma cases. The ARAF mutations were shown to transform immortalized human airway epithelial cells in a sorafenib-sensitive manner. These results suggest that mutanThe Journal of clinical investigationOncogenic and sorafenib-sensitive ARAF mutations in lung adenocarcinoma.PMC3973082U10 CA180870P30 CA016058U10 CA180794T32 CA009216T32 CA9216-31U01 CA114771U10 CA180820U24 CA114737U10 CA021115U01CA114771Amann JHorn LCarbone DPKaplan BSchiller JVillalona-Calero MAMeyerson MGreulich HImielinski MAraujo LfalseOncogenic and sorafenib-sensitive ARAF mutations in lung adenocarcinoma.Targeted cancer therapies often induce "outlier" responses in molecularly defined patient subsets. One patient with advanced-stage lung adenocarcinoma, who was treated with oral sorafenib, demonstrated a near-complete clinical and radiographic remission for 5 years. Whole-genome sequencing and RNA sequencing of primary tumor and normal samples from this patient identified a somatic mutation, ARAF S214C, present in the cancer genome and expressed at high levels. Additional mutations affecting this residue of ARAF and a nearby residue in the related kinase RAF1 were demonstrated across 1% of an independent cohort of lung adenocarcinoma cases. The ARAF mutations were shown to transform immortalized human airway epithelial cells in a sorafenib-sensitive manner. These results suggest that mutan2014-01-01T00:00:00Z2014 Apr2025-04-20T02:45:58.774Z2019-03-27T01:24:18ZS-EPMC39730822456945810.1172/jci7276310.1172/JCI72763