title: High-throughput tissue microarray analysis of 11q13 gene amplification (CCND1, FGF3, FGF4, EMS1) in urinary bladder cancer.
abstract: Gene amplification is a common mechanism for oncogene overexpression. High-level amplifications at 11q13 have been repeatedly found in bladder cancer by comparative genomic hybridization (CGH) and other techniques. Putative candidate oncogenes located in this region are CCND1 (PRAD1, bcl-1), EMS1, FGF3 (Int-2), and FGF4 (hst1, hstf1). To evaluate the involvement of these genes in bladder cancer, a tissue microarray (TMA) containing 2317 samples was screened by fluorescence in situ hybridization (FISH). The frequency of gains and amplifications of all genes increased significantly from stage pTa to pT1-4 and from low to high grade. In addition, amplification was associated with patient survival and progression of pT1 tumours. Among 123 tumours with amplifications, 68.3% showed amplification of all four genes; 19.5% amplification of CCND1, FGF4, and FGF3; and 0.8% co-amplification of FGF4, FGF3, and EMS1. Amplification of CCND1 alone was found in 9% of the tumours, while EMS1 alone was amplified in 1.6% and FGF4 in 0.8%. Overall, the amplification frequency decreased with increasing genomic distance from CCND1, suggesting that, among the genes examined, CCND1 is the major target gene in the 11q13 amplicon in bladder cancer.
authors.affiliation: Department of Medical Genetics, Medical University, Zdrave 2, 1431 Sofia, Bulgaria.
authors.forename: Boriana M
authors.initials: BM
authors.lastname: Zaharieva
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.forename: Pierre-Andre
authors.initials: PA
authors.lastname: Diener
authors.forename: Daniel
authors.initials: D
authors.lastname: Ackermann
authors.forename: Robert
authors.initials: R
authors.lastname: Maurer
authors.forename: Göran
authors.initials: G
authors.lastname: Alund
authors.forename: Hartmut
authors.initials: H
authors.lastname: Knönagel
authors.forename: Marcus
authors.initials: M
authors.lastname: Rist
authors.forename: Kim
authors.initials: K
authors.lastname: Wilber
authors.forename: Franz
authors.initials: F
authors.lastname: Hering
authors.forename: Andreas
authors.initials: A
authors.lastname: Schönenberger
authors.forename: Renata
authors.initials: R
authors.lastname: Flury
authors.forename: Peter
authors.initials: P
authors.lastname: Jäger
authors.forename: Jean Luc
authors.initials: JL
authors.lastname: Fehr
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mihatsch
authors.forename: Thomas
authors.initials: T
authors.lastname: Gasser
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.forename: Draga I
authors.initials: DI
authors.lastname: Toncheva
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018288:Carcinoma, Small Cell / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D002295:Carcinoma, Transitional Cell / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D051356:Cortactin; D019938:Cyclin D1 / Q000235:genetics; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D051518:Fibroblast Growth Factor 3; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000235:genetics; D005784:Gene Amplification / Q000235:genetics*; D019940:Genes, bcl-1 / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D009857:Oncogenes / Q000235:genetics*; D010641:Phenotype; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
chemical_list: C495868:CTTN protein, human; D051356:Cortactin; D004273:DNA, Neoplasm; C496444:FGF3 protein, human; C496445:FGF4 protein, human; D051518:Fibroblast Growth Factor 3; D051519:Fibroblast Growth Factor 4; D008840:Microfilament Proteins; D011518:Proto-Oncogene Proteins; D019938:Cyclin D1; D005346:Fibroblast Growth Factors