High-throughput tissue microarray analysis of 11q13 gene amplification (CCND1, FGF3, FGF4, EMS1) in urinary bladder cancer.
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High-throughput tissue microarray analysis of 11q13 gene amplification (CCND1, FGF3, FGF4, EMS1) in urinary bladder cancer. / Zaharieva, Boriana M; Simon, Ronald; Diener, Pierre-Andre; 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.
In: J PATHOL, Vol. 201, No. 4, 4, 2003, p. 603-608.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - High-throughput tissue microarray analysis of 11q13 gene amplification (CCND1, FGF3, FGF4, EMS1) in urinary bladder cancer.
AU - Zaharieva, Boriana M
AU - Simon, Ronald
AU - Diener, Pierre-Andre
AU - Ackermann, Daniel
AU - Maurer, Robert
AU - Alund, Göran
AU - Knönagel, Hartmut
AU - Rist, Marcus
AU - Wilber, Kim
AU - Hering, Franz
AU - Schönenberger, Andreas
AU - Flury, Renata
AU - Jäger, Peter
AU - Fehr, Jean Luc
AU - Mihatsch, Michael J
AU - Gasser, Thomas
AU - Sauter, Guido
AU - Toncheva, Draga I
PY - 2003
Y1 - 2003
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 201
SP - 603
EP - 608
JO - J PATHOL
JF - J PATHOL
SN - 0022-3417
IS - 4
M1 - 4
ER -
