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Submitted on September 26, 2001
Dept. of Clinical Biochemistry, Aarhus University hospital Skejby, Aarhus 8200
Corresponding Author: orntoft{at}kba.sks.au.dk
Summary Gain and loss of chromosomal material is characteristic of bladder cancer as well as malignant transformation in general. The consequences of these changes at both the transcription and translation levels is at present unknown partly because of technical limitations. Here, we have attempted to address this question in pairs of non-invasive and invasive human bladder tumors using a combination of technology that included comparative genomic hybridization (CGH), high density oligonucleotide array based monitoring of transcript levels (5600 genes), and high resolution two-dimensional (2D) gel electrophoresis. The results showed that there is a gene dosage effect that in some cases superimposes on other regulatory mechanisms. This effect depended (p<0.015) on the magnitude of the CGH change. In general (18 out of 23 cases), chromosomal areas with more than two fold gain of DNA showed a corresponding increase in mRNA transcripts. Areas with loss of DNA, on the other hand, showed either reduced or unaltered transcript levels. Since most proteins resolved by 2D gels are unknown it was only possible to compare mRNA and protein alterations in relatively few cases of well focused abundant proteins. With few exceptions we found a good correlation (p<0.005) between transcript alterations and protein levels. The implications as well as limitations of the approach are discussed.
Revised on November 7, 2001
Accepted on November 13, 2001
Genome wide study of gene copy numbers, transcripts and protein levels in pairs of non-invasive and invasive human transitional cell carcinomas
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