TY - CHAP
T1 - Analyzing cancer samples with SNP arrays
AU - Loo, Peter Van
AU - Nilsen, Gro
AU - Nordgard, Silje H.
AU - Vollan, Hans Kristian Moen
AU - Børresen-Dale, Anne Lise
AU - Kristensen, Vessela N.
AU - Lingjærde, Ole Christian
PY - 2012
Y1 - 2012
N2 - Single nucleotide polymorphism (SNP) arrays are powerful tools to delineate genomic aberrations in cancer genomes. However, the analysis of these SNP array data of cancer samples is complicated by three phenomena: (a) aneuploidy: due to massive aberrations, the total DNA content of a cancer cell can differ significantly from its normal two copies; (b) nonaberrant cell admixture: samples from solid tumors do not exclusively contain aberrant tumor cells, but always contain some portion of nonaberrant cells; (c) intratumor heterogeneity: different cells in the tumor sample may have different aberrations. We describe here how these phenomena impact the SNP array profile, and how these can be accounted for in the analysis. In an extended practical example, we apply our recently developed and further improved ASCAT (allele-specific copy number analysis of tumors) suite of tools to analyze SNP array data using data from a series of breast carcinomas as an example. We first describe the structure of the data, how it can be plotted and interpreted, and how it can be segmented. The core ASCAT algorithm next determines the fraction of nonaberrant cells and the tumor ploidy (the average number of DNA copies), and calculates an ASCAT profile. We describe how these ASCAT profiles visualize both copy number aberrations as well as copy-number-neutral events. Finally, we touch upon regions showing intratumor heterogeneity, and how they can be detected in ASCAT profiles. All source code and data described here can be found at our ASCAT Web site ( http://www.ifi.uio.no/forskning/grupper/bioinf/Projects/ASCAT/).
AB - Single nucleotide polymorphism (SNP) arrays are powerful tools to delineate genomic aberrations in cancer genomes. However, the analysis of these SNP array data of cancer samples is complicated by three phenomena: (a) aneuploidy: due to massive aberrations, the total DNA content of a cancer cell can differ significantly from its normal two copies; (b) nonaberrant cell admixture: samples from solid tumors do not exclusively contain aberrant tumor cells, but always contain some portion of nonaberrant cells; (c) intratumor heterogeneity: different cells in the tumor sample may have different aberrations. We describe here how these phenomena impact the SNP array profile, and how these can be accounted for in the analysis. In an extended practical example, we apply our recently developed and further improved ASCAT (allele-specific copy number analysis of tumors) suite of tools to analyze SNP array data using data from a series of breast carcinomas as an example. We first describe the structure of the data, how it can be plotted and interpreted, and how it can be segmented. The core ASCAT algorithm next determines the fraction of nonaberrant cells and the tumor ploidy (the average number of DNA copies), and calculates an ASCAT profile. We describe how these ASCAT profiles visualize both copy number aberrations as well as copy-number-neutral events. Finally, we touch upon regions showing intratumor heterogeneity, and how they can be detected in ASCAT profiles. All source code and data described here can be found at our ASCAT Web site ( http://www.ifi.uio.no/forskning/grupper/bioinf/Projects/ASCAT/).
KW - ASCAT
KW - Allelic bias
KW - Aneuploidy
KW - Cancer
KW - Intratumor heterogeneity
KW - SNP arrays
KW - Tumor
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U2 - 10.1007/978-1-61779-400-1_4
DO - 10.1007/978-1-61779-400-1_4
M3 - Chapter
C2 - 22130873
AN - SCOPUS:84555188305
SN - 9781617793998
T3 - Methods in Molecular Biology
SP - 57
EP - 72
BT - Next Generation Microarray Bioinformatics
A2 - Wang, Junbai
A2 - Tian, Tianhai
A2 - Tan, Aik Choon
ER -