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Series GSE40938 Query DataSets for GSE40938
Status Public on Aug 30, 2013
Title Detailed analysis of 6p and 1q amplifications in urothelial carcinoma reveals SOX4 as an auxiliary target on 6p, and BCL9, CHDL1, MCL1, SETDB1, and HIF1B as putative targets on 1q.
Organism Homo sapiens
Experiment type Genome variation profiling by genome tiling array
Summary Background: Previous array CGH analyses have revealed several recurring genomic alterations in urothelial carcinoma. The most common genomic amplifications occur at 6p22 and 1q21-24. The main target gene at 6p22 is believed to be E2F3. This gene is frequently co-amplified with CDKAL1 and SOX4 and there are reports on 6p22 amplifications that do not include the E2F3 locus. Previous array CGH analyses have indicated multiple possible target regions at 1q21-24. However, due to complex rearrangements it has been difficult to identify specific 1q21-24 target regions and target genes.

Results: We show that the most commonly amplified gene at 6p22 is SOX4 and that SOX4 can be amplified and over expressed without E2F3 or CDKAL1 being included in the amplicon. Hence, our data point to SOX4 as an auxiliary amplification target at 6p22. We further show that at least three amplified regions are observed at 1q21-24. Copy number data, combined with gene expression data, highlighted BCL9 and CHD1L as possible targets in the most proximal region and MCL1, SETDB1, and HIF1B as targets in the middle region, whereas no obvious gene targets could be determined in the most distal amplicon. We also highlight the enrichment of G4 quadruplex sequence motifs and the high number of intraregional sequence duplications, both known to contribute to genomic instability, as prominent features of the 1q21-24 region.

Conclusions: Our detailed analyses of the 6p22 amplicon in urothelial carcinomas suggest SOX4 as an auxiliary target gene for amplification. We further demonstrate three separate target regions for amplification at 1q21-24 and identified BCL9, CHD1L, MCL1, SETDB1, and HIF1B as likely target genes within these regions.
Overall design The study was conducted on genomic DNA from 68 primary fresh-frozen urothelial carcinoma tumors analysed using a Agilent SurePrint G3 4x180k Custom CGH Microarray Platform (028432). Samples were selected based on the presence of copy number alterations observed on lower resolution genomic data (32K BAC array).

The majority of the BAC data is publicly available in GEO submissions GSE32535 and GSE19915. CN profiles for a minority of samples were derived from Illumina Methylation27k arrays according to Lauss et al 2012 [PMID: 22705924] and can be recreated from the data deposited in GSE33510 (derived CN data). Sample names are the same between all studies.

This dataset also partly overlaps with Series GSE32894 (gene expression data). Names of the overlapping sample names are the same and indicated in the description field. Data from GSE32894 was used to calculate correlations between CN and gene expression.
Contributor(s) Eriksson P, Aine M, Lindgren D, Sjödahl G, Höglund M
Citation(s) 23825644
Submission date Sep 17, 2012
Last update date Sep 01, 2013
Contact name Mattias Aine
Phone +46-46-2220394
Organization name Lund University
Department Oncology
Lab Urothelial Cancer Genomics
Street address Klinikgatan 28
City Lund
ZIP/Postal code SE-221 84
Country Sweden
Platforms (1)
GPL16063 Agilent-028432 Human Bladder_4x180K_CGH_array (Probe Name version)
Samples (68)
GSM1005335 Urothelial Carcinoma, Sample 1
GSM1005336 Urothelial Carcinoma, Sample 2
GSM1005337 Urothelial Carcinoma, Sample 3
BioProject PRJNA175405

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE40938_RAW.tar 3.4 Gb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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