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MO15 - Novel Genes and Pathways (ID 89)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Biology
- Presentations: 1
MO15.05 - Oncogenic ARAF mutation in lung adenocarcinoma (ID 2860)
16:15 - 17:45 | Author(s): M. Imielinski
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 complete clinical and radiographic remission for five years. Whole genome sequencing (WGS) and RNA sequencing (RNA-seq) on primary tumor and normal samples from this patient was performed.
We 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 mutants were shown to transform immortalized human airway epithelial cells and were associated with in vitro sorafenib sensitivity.
These results suggest that mutant ARAF may be a novel oncogenic driver in lung adenocarcinoma and an indicator of sorafenib response.
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