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| Status |
Public on Jul 31, 2007 |
| Title |
Combined arrayCGH and SNP-loss of heterozygosity analysis in cervical cancer |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
Genome variation profiling by genome tiling array
Genome variation profiling by SNP array
SNP genotyping by SNP array
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| Summary |
BACKGROUND: Cervical carcinoma develops as a result of multiple genetic alterations. Different studies investigated genomic alterations in cervical cancer mainly by means of metaphase comparative genomic hybridization (mCGH) and microsatellite marker analysis for the detection of loss of heterozygosity (LOH). Currently, high throughput methods such as array comparative genomic hybridization (array CGH), single nucleotide polymorphism array (SNP array) and gene expression arrays are available to study genome-wide alterations. Integration of these 3 platforms allows detection of genomic alterations at high resolution and investigation of an association between copy number changes and expression. RESULTS: Genome-wide copy number and genotype analysis of 10 cervical cancer cell lines by array CGH and SNP array showed highly complex large-scale alterations. A comparison between array CGH and SNP array revealed that the overall concordance in detection of the same areas with copy number alterations (CNA) was above 90%. The use of SNP arrays demonstrated that about 75% of LOH events would not have been found by methods which screen for copy number changes, such as array CGH, since these were LOH events without CNA. Regions frequently targeted by CNA, as determined by array CGH, such as amplification of 5p and 20q, and loss of 8p were confirmed by fluorescent in situ hybridization (FISH). Genome-wide, we did not find a correlation between copy-number and gene expression. At chromosome arm 5p however, 22% of the genes were significantly upregulated in cell lines with amplifications as compared to cell lines without amplifications, as measured by gene expression arrays. For 3 genes, SKP2, ANKH and TRIO, expression differences were confirmed by quantitative real-time PCR (qRT-PCR). CONCLUSION: This study showed that copy number data retrieved from either array CGH or SNP array are comparable and that the integration of genome-wide LOH, copy number and gene expression is useful for the identification of gene specific targets that could be relevant for the development and progression in cervical cancer.
Keywords: DNA copynumber RNA expression correlation
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| Overall design |
Cervival cancer cell lines were hybridized to Affymetrix Focus arrays in duplicate. Correlations were made with copynumber profiles from arrayCGH and SNP arrays.
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| Contributor(s) |
Kloth JN, Oosting J, van Wezel T, Szuhai K, Knijnenburg J, Gorter A, Kenter GG, Fleuren G, Jordanova ES |
| Citation(s) |
17311676 |
| Submission date |
Jul 27, 2007 |
| Last update date |
Jul 08, 2016 |
| Contact name |
Jan Oosting |
| Phone |
+31 71 5266619
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| Organization name |
Leiden University Medical Center
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| Department |
Pathology
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| Street address |
Albinusdreef 2
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| City |
Leiden |
| ZIP/Postal code |
2333ZA |
| Country |
Netherlands |
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| Platforms (3) |
| GPL201 |
[HG-Focus] Affymetrix Human HG-Focus Target Array |
| GPL2641 |
[Mapping10K_Xba142] Affymetrix Human Mapping 10K 2.0 Array |
| GPL4012 |
3.7k full genome LUMC BAC array |
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| Samples (40)
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| Relations |
| BioProject |
PRJNA101773 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE8605_RAW.tar |
53.4 Mb |
(http)(custom) |
TAR (of CEL, GPR) |
| Processed data included within Sample table |
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