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Cancer Discov. 2013 Jun;3(6):636-47. doi: 10.1158/2159-8290.CD-13-0050. Epub 2013 Apr 4.

Identification of targetable FGFR gene fusions in diverse cancers.

Author information

1
Michigan Center for Translational Pathology, University of Michigan Medical School, 1400 E. Medical Center Drive 5316 CCGC, Ann Arbor, MI 48109-5940, USA.

Abstract

Through a prospective clinical sequencing program for advanced cancers, four index cases were identified which harbor gene rearrangements of FGFR2, including patients with cholangiocarcinoma, breast cancer, and prostate cancer. After extending our assessment of FGFR rearrangements across multiple tumor cohorts, we identified additional FGFR fusions with intact kinase domains in lung squamous cell cancer, bladder cancer, thyroid cancer, oral cancer, glioblastoma, and head and neck squamous cell cancer. All FGFR fusion partners tested exhibit oligomerization capability, suggesting a shared mode of kinase activation. Overexpression of FGFR fusion proteins induced cell proliferation. Two bladder cancer cell lines that harbor FGFR3 fusion proteins exhibited enhanced susceptibility to pharmacologic inhibition in vitro and in vivo. Because of the combinatorial possibilities of FGFR family fusion to a variety of oligomerization partners, clinical sequencing efforts, which incorporate transcriptome analysis for gene fusions, are poised to identify rare, targetable FGFR fusions across diverse cancer types.

PMID:
23558953
PMCID:
PMC3694764
DOI:
10.1158/2159-8290.CD-13-0050
[Indexed for MEDLINE]
Free PMC Article

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