High-throughput tissue microarray analysis of 11q13 gene amplification (CCND1, FGF3, FGF4, EMS1) in urinary bladder cancer.
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.
Zaharieva
Boriana M
BM
Department of Medical Genetics, Medical University, Zdrave 2, 1431 Sofia, Bulgaria.
Simon
Ronald
R
Diener
Pierre-Andre
PA
Ackermann
Daniel
D
Maurer
Robert
R
Alund
Göran
G
Knönagel
Hartmut
H
Rist
Marcus
M
Wilber
Kim
K
Hering
Franz
F
Schönenberger
Andreas
A
Flury
Renata
R
Jäger
Peter
P
Fehr
Jean Luc
JL
Mihatsch
Michael J
MJ
Gasser
Thomas
T
Sauter
Guido
G
Toncheva
Draga I
DI
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*
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