title: Fibroblastic growth factor receptor 1 amplification in osteosarcoma is associated with poor response to neo-adjuvant chemotherapy.
abstract: Osteosarcoma, the most common primary bone sarcoma, is a genetically complex disease with no widely accepted biomarker to allow stratification of patients for treatment. After a recent report of one osteosarcoma cell line and one tumor exhibiting fibroblastic growth factor receptor 1 (FGFR1) gene amplification, the aim of this work was to assess the frequency of FGFR1 amplification in a larger cohort of osteosarcoma and to determine if this biomarker could be used for stratification of patients for treatment. About 352 osteosarcoma samples from 288 patients were analyzed for FGFR1 amplification by interphase fluorescence in situ hybridization. FGFR1 amplification was detected in 18.5% of patients whose tumors revealed a poor response to chemotherapy, and no patients whose tumors responded well to therapy harbored this genetic alteration. FGFR1 amplification is present disproportionately in the rarer histological variants of osteosarcoma. This study provides a rationale for inclusion of patients with osteosarcoma in clinical trials using FGFR kinase inhibitors.
authors.affiliation: Histopathology, London Sarcoma Service, Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex, HA7 4LP, U.K; UCL Cancer Institute, Huntley Street, London, WC1E 6BT, U.K.
authors.forename: M
authors.initials: M
authors.lastname: Fernanda Amary
authors.forename: Hongtao
authors.initials: H
authors.lastname: Ye
authors.forename: Fitim
authors.initials: F
authors.lastname: Berisha
authors.forename: Bhavisha
authors.initials: B
authors.lastname: Khatri
authors.forename: Georgina
authors.initials: G
authors.lastname: Forbes
authors.forename: Katie
authors.initials: K
authors.lastname: Lehovsky
authors.forename: Anna M
authors.initials: AM
authors.lastname: Frezza
authors.forename: Sam
authors.initials: S
authors.lastname: Behjati
authors.forename: Patrick
authors.initials: P
authors.lastname: Tarpey
authors.forename: Nischalan
authors.initials: N
authors.lastname: Pillay
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Campbell
authors.forename: Roberto
authors.initials: R
authors.lastname: Tirabosco
authors.forename: Nadège
authors.initials: N
authors.lastname: Presneau
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Strauss
authors.forename: Adrienne M
authors.initials: AM
authors.lastname: Flanagan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics*; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1
keywords: Amplification; FGFR; FGFR1; FISH; genetics; osteosarcoma; polysomy