Detection limits of DNA copy number alterations in heterogeneous cell populations
| Autor: | Aggie W. M. Nieuwint, Michel L. M. Berens, Clemens Mellink, Gerrit A. Meijer, Marjan M. Weiss, Hendrik F. van Essen, Oscar Krijgsman, Renske D.M. Steenbergen, Bauke Ylstra, Paul P. Eijk, Danielle Israeli |
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| Přispěvatelé: | Pathology, Human genetics, CCA - Disease profiling, Human Genetics |
| Rok vydání: | 2013 |
| Předmět: |
Cancer Research
DNA Copy Number Variations Microarray Population Copy number analysis Breast Neoplasms Biology Genome chemistry.chemical_compound Cell Line Tumor Intellectual Disability Humans education In Situ Hybridization Fluorescence Oligonucleotide Array Sequence Analysis Chromosome Aberrations Comparative Genomic Hybridization education.field_of_study Oligonucleotide Reproducibility of Results DNA General Medicine Leukemia Lymphocytic Chronic B-Cell Molecular biology Oncology chemistry Molecular Medicine Female DNA microarray Comparative genomic hybridization |
| Zdroj: | Cellular Oncology, 36(1), 27-36. IOS Press Krijgsman, O, Israeli, D, van Essen, H F B, Eijk, P P, Berens, M L M, Mellink, C H M, Nieuwint, A W M, Weiss, M M, Steenbergen, R D M, Meijer, G A & Ylstra, B 2013, ' Detection limits of DNA copy number alterations in heterogeneous cell populations ', Cellular Oncology, vol. 36, no. 1, pp. 27-36 . https://doi.org/10.1007/s13402-012-0108-2 Cellular oncology (Dordrecht), 36(1), 27-36. IOS Press |
| ISSN: | 2211-3428 1875-8606 |
| DOI: | 10.1007/s13402-012-0108-2 |
| Popis: | 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. Here we evaluated to what extent aCGH can detect DNA copy number alterations in heterogeneous cell populations. A systematic evaluation is currently lacking, despite its importance in diagnostics and research. The detection limits reported are a compound of analytical software and laboratory techniques and do not account for the number of probes in relation to sample homogeneity. 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 microarrays containing 180,880 oligonucleotides evenly distributed over the genome (spacing similar to 17 kb). Single copy number alterations, represented by down to 249 probes (4 Mb) and present in 10 % of a cell population, could be detected. Alterations encompassing as few as 14 probes (similar to 238 Kb) could also be detected, but for this a 35 % mosaic level was required. DNA copy number alterations can be detected in cell populations containing 10 % abnormal cells. Detection of sub-megabase alterations requires a higher percentage of abnormal cells or microarrays with a higher probe density |
| Databáze: | OpenAIRE |
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