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:Search for copy number imbalances and allelotype in 971 early stage breast cancer using molecular inversion probe arrays Affymetrix MIP arrays were performed according to the manufacturer's directions on DNA extracted from paraffin embedded formalin fixed Stage I and II Breast Cancers Copy number analysis of Affymetrix Oncoscan Version 1 MIP arrays was performed for 971 Stage I and II breast cancers.
Project description:DNA copy number changes with or without accompanying copy neutral changes such as unparental disomy (UPD) is a feature of the cancer genome that is linked to cancer development. However, technical problems with archived formalin-fixed, paraffin-embedded (FFPE) tissue samples have limited their general use in genomic profiling studies done using high-density single nucleotide polymorphism (SNP) microarray. To overcome the current problems with the use of this material in the detection of DNA copy number and copy neutral changes, we have devised two new protocols for extracting DNA from FFPE tissue. Genotyping efficiency and accuracy were improved using our novel protocols. After censoring the larger fragments, we obtained call rates for FFPE DNA equivalent to those for FF tissue DNA, with concordance rates between FFPE and FF tumor exceeding 99%. Identical DNA copy number changes were obtained for FFPE and FF; and between two new extraction protocols in tumor samples by using Affymetrix® high-density oligo-based SNP microarray platform. We observed UPD and recurrent gains and losses in tumor samples. Interestingly, we also identified UPD in the 5q and 13q regions in matching normal blood, FF adjacent breast tissue and tumor tissue in two samples. In conclusion, our new two DNA extraction protocols should substantially improve the ability to use archived material to help elucidate the complexity of early-stage breast cancer genomes. Keywords: SNP based array
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.