Reference Detail

Ref Type Journal Article
PMID (25294908)
Authors Capelletti M, Dodge ME, Ercan D, Hammerman PS, Park SI, Kim J, Sasaki H, Jablons DM, Lipson D, Young L, Stephens PJ, Miller VA, Lindeman NI, Munir KJ, Richards WG, Jänne PA
Title Identification of recurrent FGFR3-TACC3 fusion oncogenes from lung adenocarcinoma.
Journal Clinical cancer research : an official journal of the American Association for Cancer Research
Vol 20
Issue 24
Date 2014 Dec 15
URL
Abstract Text Targetable oncogenic alterations are detected more commonly in patients with non-small cell lung cancer (NSCLC) who never smoked cigarettes. For such patients, specific kinase inhibitors have emerged as effective clinical treatments. However, the currently known oncogenic alterations do not account for all never smokers who develop NSCLC. We sought to identify additional oncogenic alterations from patients with NSCLC to define additional treatment options.We analyzed 576 lung adenocarcinomas from patients of Asian and Caucasian ethnicity. We identified a subset of cancers that did not harbor any known oncogenic alteration. We performed targeted next-generation sequencing (NGS) assay on 24 patients from this set with >75% tumor cell content.EGFR mutations were the most common oncogenic alteration from both Asian (53%) and Caucasian (41.6%) patients. No known oncogenic alterations were present in 25.7% of Asian and 31% of Caucasian tumor specimens. We identified a FGFR3-TACC3 fusion event in one of 24 patients from this subset using targeted NGS. Two additional patients harboring FGFR3-TACC3 were identified by screening our entire cohort (overall prevalence, 0.5%). Expression of FGFR3-TACC3 led to IL3 independent growth in Ba/F3 cells. These cells were sensitive to pan-fibroblast growth factor receptor (pan-FGFR) inhibitors but not the epidermal growth factor (EGFR) inhibitor gefitinib.FGFR3-TACC3 rearrangements occur in a subset of patients with lung adenocarcinoma. Such patients should be considered for clinical trials featuring FGFR inhibitors.

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Molecular Profile Treatment Approach
FGFR3-TACC3 FGFR Inhibitor (Pan)
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Variant Impact Protein Effect Variant Description Associated with drug Resistance
FGFR3 - TACC3 fusion gain of function FGFR3-TACC3 results from the fusion of FGFR3 and TACC3, demonstrating constitutive kinase activity, transforming activity in culture and ability to drive tumor growth in xenografts (PMID: 25294908, PMID: 22837387).
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FGFR3-TACC3 lung adenocarcinoma sensitive BGJ398 Preclinical Actionable In a preclinical study, BGJ398 inhibited growth and FGFR3 phosphorylation in cells expressing FGFR3-TACC3 fusion in culture (PMID: 25294908). 25294908
FGFR3-TACC3 lung adenocarcinoma sensitive Ponatinib Preclinical Actionable In a preclinical study, Iclusig (ponatanib) inhibited growth and FGFR3 phosphorylation in cells expressing FGFR3-TACC3 fusion in culture (PMID: 25294908). 25294908