Project description:This SuperSeries is composed of the following subset Series: GSE14740: FFPE study using MIP copy number platform - kidney GSE14741: FFPE study using MIP copy number platform - bladder/colorectal/kidney/liver GSE14742: FFPE study using MIP copy number platform - colorectal GSE14743: FFPE study using MIP copy number platform - breast cancer I GSE14744: FFPE study using MIP copy number platform - breast cancer II GSE14745: FFPE study using MIP copy number platform - liver Refer to individual Series, GSE14856_quartets.txt contains list of matched samples
Project description:We sought to test the hypothesis that ascertainment of genome-wide copy number alterations in bladder cancer may have value for clinical management. We performed a genome wide analysis of 164 bladder cancer samples and 27 bladder cancer cell lines to identify genetic changes associated with disease characteristics. Multiplex inversion probe (MIP) analysis, a newly developed genomic technique, was used to study 80 bladder cancers to identify mutations and copy number changes. Selected amplification events were then analyzed in a validation cohort of 84 bladder cancers by multiplex ligation-dependent probe assay (MLPA). In the MIP analysis, 44 regions of significant copy number change were identified using GISTIC. Nine gene-containing regions of amplification were selected for validation in the second cohort by MLPA. Amplification events at these 9 genomic regions were found to correlate strongly with stage, being seen in only 2 of 23 (9%) Ta grade 1 or 1-2 cancers, in contrast to 31 of 61 (51%) Ta grade 3 and T2 grade 2 cancers, p < 0.001. These observations suggest that analysis of genomic amplification of these 9 regions might serve as a guide for clinical decision making, in terms of management decisions following transurethral resection of bladder cancers. This approach is facilitated by the capability of each of the MIP and MLPA methods to analyze formalin-fixed paraffin-embedded DNA, as done here. Furthermore several of the amplified genes identified here (ERBB2, MDM2, CCND1) render the bladder cancers potentially sensitive to targeted therapy. Copy number profiling was completed for 80 urothelial carcinoma samples using the Affymetrix OncoScan(TM) FFPE Express platform.
Project description:We sought to test the hypothesis that ascertainment of genome-wide copy number alterations in bladder cancer may have value for clinical management. We performed a genome wide analysis of 164 bladder cancer samples and 27 bladder cancer cell lines to identify genetic changes associated with disease characteristics. Multiplex inversion probe (MIP) analysis, a newly developed genomic technique, was used to study 80 bladder cancers to identify mutations and copy number changes. Selected amplification events were then analyzed in a validation cohort of 84 bladder cancers by multiplex ligation-dependent probe assay (MLPA). In the MIP analysis, 44 regions of significant copy number change were identified using GISTIC. Nine gene-containing regions of amplification were selected for validation in the second cohort by MLPA. Amplification events at these 9 genomic regions were found to correlate strongly with stage, being seen in only 2 of 23 (9%) Ta grade 1 or 1-2 cancers, in contrast to 31 of 61 (51%) Ta grade 3 and T2 grade 2 cancers, p < 0.001. These observations suggest that analysis of genomic amplification of these 9 regions might serve as a guide for clinical decision making, in terms of management decisions following transurethral resection of bladder cancers. This approach is facilitated by the capability of each of the MIP and MLPA methods to analyze formalin-fixed paraffin-embedded DNA, as done here. Furthermore several of the amplified genes identified here (ERBB2, MDM2, CCND1) render the bladder cancers potentially sensitive to targeted therapy.