Oncogenic and sorafenib-sensitive ARAF mutations in lung adenocarcinoma

Marcin Imielinski, Heidi Greulich, Bethany Kaplan, Luiz Araujo, Joseph Amann, Leora Horn, Joan Schiller, Miguel A. Villalona-Calero, Matthew Meyerson, David P. Carbone

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1582-1586
Number of pages5
JournalJournal of Clinical Investigation
Volume124
Issue number4
DOIs
StatePublished - Apr 1 2014

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Mutation
Genome
RNA Sequence Analysis
Neoplasms
Phosphotransferases
Epithelial Cells
sorafenib
Adenocarcinoma of lung
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Imielinski, M., Greulich, H., Kaplan, B., Araujo, L., Amann, J., Horn, L., ... Carbone, D. P. (2014). Oncogenic and sorafenib-sensitive ARAF mutations in lung adenocarcinoma. Journal of Clinical Investigation, 124(4), 1582-1586. https://doi.org/10.1172/JCI72763

Oncogenic and sorafenib-sensitive ARAF mutations in lung adenocarcinoma. / Imielinski, Marcin; Greulich, Heidi; Kaplan, Bethany; Araujo, Luiz; Amann, Joseph; Horn, Leora; Schiller, Joan; Villalona-Calero, Miguel A.; Meyerson, Matthew; Carbone, David P.

In: Journal of Clinical Investigation, Vol. 124, No. 4, 01.04.2014, p. 1582-1586.

Research output: Contribution to journalArticle

Imielinski, M, Greulich, H, Kaplan, B, Araujo, L, Amann, J, Horn, L, Schiller, J, Villalona-Calero, MA, Meyerson, M & Carbone, DP 2014, 'Oncogenic and sorafenib-sensitive ARAF mutations in lung adenocarcinoma', Journal of Clinical Investigation, vol. 124, no. 4, pp. 1582-1586. https://doi.org/10.1172/JCI72763
Imielinski M, Greulich H, Kaplan B, Araujo L, Amann J, Horn L et al. Oncogenic and sorafenib-sensitive ARAF mutations in lung adenocarcinoma. Journal of Clinical Investigation. 2014 Apr 1;124(4):1582-1586. https://doi.org/10.1172/JCI72763
Imielinski, Marcin ; Greulich, Heidi ; Kaplan, Bethany ; Araujo, Luiz ; Amann, Joseph ; Horn, Leora ; Schiller, Joan ; Villalona-Calero, Miguel A. ; Meyerson, Matthew ; Carbone, David P. / Oncogenic and sorafenib-sensitive ARAF mutations in lung adenocarcinoma. In: Journal of Clinical Investigation. 2014 ; Vol. 124, No. 4. pp. 1582-1586.
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