Oncogenic and sorafenib-sensitive ARAF mutations in lung adenocarcinoma Academic Article uri icon

Overview

MeSH Major

  • Adenocarcinoma
  • Antineoplastic Agents
  • Lung Neoplasms
  • Mutation, Missense
  • Niacinamide
  • Phenylurea Compounds
  • Proto-Oncogene Proteins A-raf

abstract

  • 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 mutant ARAF is an oncogenic driver in lung adenocarcinoma and an indicator of sorafenib response.

publication date

  • April 2014

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3973082

Digital Object Identifier (DOI)

  • 10.1172/JCI72763

PubMed ID

  • 24569458

Additional Document Info

start page

  • 1582

end page

  • 6

volume

  • 124

number

  • 4