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| Status |
Public on Oct 21, 2012 |
| Title |
Ten percent of aberrant cells is sufficient for detection of DNA copy number alterations (part 2) |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by genome tiling array
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| Summary |
Array Comparative Genomic Hybridization (aCGH) is a widely used technique to assess chromosomal copy number alterations. Chromosomal content, however, is often not uniform throughout cell populations. The aim of our present study is to evaluate to what extent aCGH can detect DNA copy number alterations in a heterogeneous cell population. Reported detection limits are a compound of analytical software and laboratory technique whilst systematic evaluation is lacking, despite the importance in diagnostics and research. Detection limits were explored with DNA isolated from a patient with intellectual disability (ID) and from tumor cell line BT474. Both were diluted with increasing amounts of normal DNA to simulate different levels of cellularity. Samples were hybridized on CGH arrays containing 180880 oligonucleotides evenly distributed over the genome (space ~17kb). The ID sample has a single copy number gain of 4Mb and a single copy number loss of 7.5Mb that could both be detected with 10% mosaicism. The tumor cell line BT474 has a dual copy number gain (6 copies in a background of 4 copies) of 46Mb. This corresponds to a single copy number gain in a diploid sample and could be detected with 15% tumor cells. The diagnostic validity of these findings was verified using two clinical mosaic samples with alterations in 20% (40Mb) and 14% (34Mb) of cells. Both alterations could be accurately detected using t-statistics. In conclusion, single copy number gains and losses, down to 4Mb in as little as 10% of a cell population, can be detected by aCGH.
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| Overall design |
Dilution range of breast cancer cell line BT474.
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| Contributor(s) |
Krijgsman O, Israeli D, van Essen HF, Eijk PP, Berens ML, Mellink CH, Nieuwint AW, Weiss M, Steenbergen RD, Meijer GA, Ylstra B |
| Citation(s) |
23117839 |
| |
| Submission date |
Apr 02, 2012 |
| Last update date |
Nov 05, 2012 |
| Contact name |
Daoud Sie |
| E-mail(s) |
[email protected]
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| Phone |
+31 20 4442428
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| Organization name |
Vrije Universiteit Medical Center
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| Department |
Pathology
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| Lab |
Microarray Core Facility
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| Street address |
De Boelelaan 1117
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| City |
Amsterdam |
| ZIP/Postal code |
1081 HV |
| Country |
Netherlands |
| |
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| Platforms (1) |
| GPL10197 |
Nimblegen Human 12x135K array [090527_HG18_WG_CGH_v3.1_HX12] |
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| Samples (14)
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| This SubSeries is part of SuperSeries: |
| GSE36993 |
Ten percent of aberrant cells is sufficient for detection of DNA copy number alterations |
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| Relations |
| BioProject |
PRJNA157473 |
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