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Clin Cancer Res. 2014 Dec 15;20(24):6551-8. doi: 10.1158/1078-0432.CCR-14-1337. Epub 2014 Oct 7.

Identification of recurrent FGFR3-TACC3 fusion oncogenes from lung adenocarcinoma.

Author information

1
Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
2
Department of Thoracic Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
3
Department of Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
4
Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
5
Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California.
6
Foundation Medicine, Inc., Cambridge, Massachusetts.
7
Department of Pathology and Center for Advanced Molecular Diagnostics, Brigham and Women's Hospital, Boston, Massachusetts.
8
Division of Thoracic Surgery, Brigham and Women's Hospital, Boston, Massachusetts.
9
Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts. pasi_janne@dfci.harvard.edu.

Abstract

PURPOSE:

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.

EXPERIMENTAL DESIGN:

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.

RESULTS:

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.

CONCLUSIONS:

FGFR3-TACC3 rearrangements occur in a subset of patients with lung adenocarcinoma. Such patients should be considered for clinical trials featuring FGFR inhibitors.

PMID:
25294908
DOI:
10.1158/1078-0432.CCR-14-1337
[Indexed for MEDLINE]
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