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Series GSE6473 Query DataSets for GSE6473
Status Public on Oct 20, 2008
Title Integrated genomic and transcriptional profiling yields putative marker genes for cervical cancer
Organism Homo sapiens
Experiment type Genome variation profiling by genome tiling array
Expression profiling by genome tiling array
Summary A better understanding of the consequences of recurrent (epi)genetic alterations that occur during cervical carcinogenesis is essential in the search for novel biomarkers. In this study we determined genome-wide expression profiles of 10 squamous cell carcinomas (SCCs), 5 adenocarcinomas (AdCAs) and 6 normal epithelial samples. Expression patterns were subsequently combined with previously determined chromosomal profiles in the same carcinomas.
Differential gene expression analysis identified 76 genes with altered expression in carcinomas compared to normal epithelium. Microarray results for a subset of these genes were validated by real-time RT-PCR. Among the differentially expressed genes a relative overrepresentation of genes located at chromosome 3q, one of the most frequently gained areas in SCCs, was observed (false discovery rate (FDR)<0.005). To further investigate the relationship between gene expression and chromosomal alterations 2 statistical approaches were used, i.e. differential gene locus mapping (DIGMAP) and the array CGH expression integration tool (ACE-it). Using these methods we found that increased gene expression was linked to increased gene copy numbers at 1q32.1, 3q13.32-22.3, 3q26.32-27.3, and 20q11.21-13.33, whereas a loss at 11q22.3-25 correlated with recurrent decreased gene expression.
Integrated genome-wide chromosomal and transcriptional analysis of cervical carcinomas highlighted 7 genes (i.e. FLJ21291, DTX3L, CCDC14, MCM2, PIK3R4, ATP2C1 and SLC25A36), which were identified by differential gene expression analysis and were located within the chromosomal regions identified by DIGMAP and/or ACE-it as well. Further investigations of these promising marker genes in warranted.
Keywords: microarray analysis, array CGH, cervical cancer
 
Overall design For microarray mRNA expression analysis 10 SCCs, 5 AdCAs and 6 normal epithelial controls were used. Normal cervical controls consisted of 1 pool of 3 normal cervices distant from tumour, 1 pool of 4 normal ectocervical smears and 1 pool of 5 normal endocervical smears. To expand our number of normal squamous epithelial controls, we included expression profiles of 3 uvulas of non-cancer patients who underwent uvulopalatopharyngoplasty. In addition, we hybridised RNA isolated from 2 different biopsies of the same SCC (SCC12 and SCC13) as a biological replicate. The pool of 4 normal ectocervical smears was hybridised twice as a technical replicate to determine technical variation.
Genomic profiling of the same 10 SCCs and 5 AdCAs was done using array CGH (Wilting et al, J Pathol 2006, volume 209, p 220-30).
 
Contributor(s) Wilting SM, de Wilde J, Meijer CJ, Berkhof J, Yi Y, van Wieringen WN, Braakhuis BJ, Ylstra B, Snijders PJ, Steenbergen RD
Citation(s) 18618715
Submission date Dec 07, 2006
Last update date Mar 16, 2012
Contact name Daoud Sie
E-mail(s) d.sie@vumc.nl
Phone +31 20 4442428
Organization name Vrije Universiteit Medical Center
Department Pathology
Lab Microarray Core Facility
Street address De Boelelaan 1117
City Amsterdam
ZIP/Postal code 1081 HV
Country Netherlands
 
Platforms (2)
GPL3054 VUMC MACF human 19K oligo v5
GPL3441 VUMC MACF human 5K BAC v12
Samples (38)
GSM148861 Uterine cervix adenoarcinoma VUMC_CxAdCA1_b7_s14
GSM148862 Uterine cervix adenocarcinoma VUMC_CxAdCA10_b7_s16
GSM148863 Uterine cervix adenocarcinoma VUMC_CxAdCA11_b7_s17
Relations
BioProject PRJNA98709

Download family Format
SOFT formatted family file(s) SOFTHelp
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Supplementary data files not provided
Processed data included within Sample table
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