Segmentation-based detection of allelic imbalance and loss-of-heterozygosity in cancer cells using whole genome SNP arrays

Johan Staaf1,2, David Lindgren, Johan Vallon-Christersson2,1, Anders Isaksson3, Hanna Göransson3, Gunnar Juliusson4, Richard Rosenquist5, Mattias Höglund1, Åke Borg2,1,4, Markus Ringnér2,1
1Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden
2CREATE Health Strategic Centre for Clinical Cancer Research, Lund University, Lund, Sweden
3Department of Medical Sciences, Cancer Pharmacology and Informatics, Uppsala University, Uppsala, Sweden
4Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden
5Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden

Tóm tắt

We present a strategy for detection of loss-of-heterozygosity and allelic imbalance in cancer cells from whole genome single nucleotide polymorphism genotyping data. Using a dilution series of a tumor cell line mixed with its paired normal cell line and data generated on Affymetrix and Illumina platforms, including paired tumor-normal samples and tumors characterized by fluorescent in situ hybridization, we demonstrate a high sensitivity and specificity of the strategy for detecting both minute and gross allelic imbalances in heterogeneous tumor samples.

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