title: Recurrent FGFR1 amplification and high FGFR1 protein expression in oral squamous cell carcinoma (OSCC).
abstract: Chromosomal aberrations are known to have an impact on the initiation and progression of oral squamous cell carcinoma (OSCC), but individual genes involved in OSCC pathogenesis are poorly described. To elucidate the molecular events underlying oral carcinogenesis, a set of primary OSCC were screened for distinct genetic imbalances by means of array-based comparative genomic hybridisation. For this, a DNA array was used containing 812 genomic targets including oncogenes, tumour-suppressor genes and chromosomal regions frequently altered in human neoplasms. The most frequent aberrations were amplification of MYC, EGFR, CCND1 and PIK3CA, whereas deletions affected TRAILR1 and ATM. Furthermore, a distinct high-level amplification of the fibroblast growth factor receptor 1 (FGFR1) locus was detected in two cases. Detailed FISH analysis on OSCC tissue microarray sections revealed amplification prevalence for FGFR1 of 17.4% (16/92). Furthermore, FGFR1 protein analysis by immunohistochemistry on a TMA containing 178 OSCC found a high FGFR1 expression in tumours of early t-stadium and UICC stage (T1/2 vs. T3/4: p=0.002; SI-II vs. S III-IV: p=0.048). Our results indicate that an increase in FGFR1 expression contributes to oral carcinogenesis at an early stage of development.
authors.affiliation: Abteilung Molekulare Genetik (B060), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. K.Freier@DKFZ.de
authors.forename: Kolja
authors.initials: K
authors.lastname: Freier
authors.forename: Carsten
authors.initials: C
authors.lastname: Schwaenen
authors.forename: Carsten
authors.initials: C
authors.lastname: Sticht
authors.forename: Christa
authors.initials: C
authors.lastname: Flechtenmacher
authors.forename: Joachim
authors.initials: J
authors.lastname: Mühling
authors.forename: Christof
authors.initials: C
authors.lastname: Hofele
authors.forename: Bernhard
authors.initials: B
authors.lastname: Radlwimmer
authors.forename: Peter
authors.initials: P
authors.lastname: Lichter
authors.forename: Stefan
authors.initials: S
authors.lastname: Joos
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D051496:Receptor, Fibroblast Growth Factor, Type 1