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High‐throughput tissue microarray analysis of 11q13 gene amplification (CCND1, FGF3, FGF4, EMS1) in urinary bladder cancer
Author(s) -
Zaharieva Boriana M,
Simon Ronald,
Diener PierreAndre,
Ackermann Daniel,
Maurer Robert,
Alund Göran,
Knönagel Hartmut,
Rist Marcus,
Wilber Kim,
Hering Franz,
Schönenberger Andreas,
Flury Renata,
Jäger Peter,
Fehr Jean Luc,
Mihatsch Michael J,
Gasser Thomas,
Sauter Guido,
Toncheva Draga I
Publication year - 2003
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1481
Subject(s) - amplicon , gene duplication , fluorescence in situ hybridization , biology , bladder cancer , gene , oncogene , cancer , microbiology and biotechnology , tissue microarray , cancer research , genetics , polymerase chain reaction , cell cycle , chromosome
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. Putitative 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. Copyright © 2003 John Wiley & Sons, Ltd.