title: Identification of targetable FGFR gene fusions in diverse cancers.
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.
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan Medical School, 1400 E. Medical Center Drive 5316 CCGC, Ann Arbor, MI 48109-5940, USA.
authors.forename: Yi-Mi
authors.initials: YM
authors.lastname: Wu
authors.forename: Fengyun
authors.initials: F
authors.lastname: Su
authors.forename: Shanker
authors.initials: S
authors.lastname: Kalyana-Sundaram
authors.forename: Nickolay
authors.initials: N
authors.lastname: Khazanov
authors.forename: Bushra
authors.initials: B
authors.lastname: Ateeq
authors.forename: Xuhong
authors.initials: X
authors.lastname: Cao
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lonigro
authors.forename: Pankaj
authors.initials: P
authors.lastname: Vats
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Su-Fang
authors.initials: SF
authors.lastname: Lin
authors.forename: Ann-Joy
authors.initials: AJ
authors.lastname: Cheng
authors.forename: Lakshmi P
authors.initials: LP
authors.lastname: Kunju
authors.forename: Javed
authors.initials: J
authors.lastname: Siddiqui
authors.forename: Scott A
authors.initials: SA
authors.lastname: Tomlins
authors.forename: Peter
authors.initials: P
authors.lastname: Wyngaard
authors.forename: Seth
authors.initials: S
authors.lastname: Sadis
authors.forename: Sameek
authors.initials: S
authors.lastname: Roychowdhury
authors.forename: Maha H
authors.initials: MH
authors.lastname: Hussain
authors.forename: Felix Y
authors.initials: FY
authors.lastname: Feng
authors.forename: Mark M
authors.initials: MM
authors.lastname: Zalupski
authors.forename: Moshe
authors.initials: M
authors.lastname: Talpaz
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Pienta
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Rhodes
authors.forename: Dan R
authors.initials: DR
authors.lastname: Robinson
authors.forename: Arul M
authors.initials: AM
authors.lastname: Chinnaiyan
mesh_terms: D000818:Animals; D050939:Gene Fusion; D055785:Gene Knockdown Techniques; D015321:Gene Rearrangement; D057166:High-Throughput Screening Assays; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D011446:Prospective Studies; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D023041:Xenograft Model Antitumor Assays
chemical_list: D015514:Oncogene Proteins, Fusion; D017468:Receptors, Fibroblast Growth Factor
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