title: Fibroblast growth factor family aberrations in cancers: clinical and molecular characteristics.
abstract: Fibroblast growth factor ligands and receptors (FGF and FGFR) play critical roles in tumorigenesis, and several drugs have been developed to target them. We report the biologic correlates of FGF/FGFR abnormalities in diverse malignancies. The medical records of patients with cancers that underwent targeted next generation sequencing (182 or 236 cancer-related genes) were reviewed. The following FGF/FGFR genes were tested: FGF3, 4, 6, 7, 10, 12, 14, 19, 23 and FGFR1, 2, 3, and 4. Of 391 patients, 56 (14.3%) had aberrant FGF (N = 38, all amplifications) and/or FGFR (N = 22 including 5 mutations and one FGFR3-TACC3 fusion). FGF/FGFR aberrations were most frequent in breast cancers (26/81, 32.1%, p = 0.0003). In multivariate analysis, FGF/FGFR abnormalities were independently associated with CCND1/2, RICTOR, ZNF703, RPTOR, AKT2, and CDK8 alterations (all P < 0.02), as well as with an increased median number of alterations (P < 0.0001). FGF3, FGF4, FGF19 and CCND1 were co-amplified in 22 of 391 patients (5.6%, P < 0.0001), most likely because they co-localize on the same chromosomal region (11q13). There was no significant difference in time to metastasis or overall survival when comparing patients harboring FGF/FGFR alterations versus those not. Overall, FGF/FGFR was one of the most frequently aberrant pathways in our population comprising patients with diverse malignancies. These aberrations frequently co-exist with anomalies in a variety of other genes, suggesting that tailored combination therapy may be necessary in these patients.
authors.affiliation: a Center for Personalized Cancer Therapy; University of California San Diego; Moores Cancer Center ; San Diego , CA , USA.
authors.forename: A
authors.initials: A
authors.lastname: Parish
authors.forename: M
authors.initials: M
authors.lastname: Schwaederle
authors.forename: G
authors.initials: G
authors.lastname: Daniels
authors.forename: D
authors.initials: D
authors.lastname: Piccioni
authors.forename: P
authors.initials: P
authors.lastname: Fanta
authors.forename: R
authors.initials: R
authors.lastname: Schwab
authors.forename: K
authors.initials: K
authors.lastname: Shimabukuro
authors.forename: B A
authors.initials: BA
authors.lastname: Parker
authors.forename: T
authors.initials: T
authors.lastname: Helsten
authors.forename: R
authors.initials: R
authors.lastname: Kurzrock
mesh_terms: D000368:Aged; D005260:Female; D005346:Fibroblast Growth Factors / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism*; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors
keywords: cancer, FGF, FGFR, sequencing, profiling