Allele-specific copy number analysis of tumors

• DOI: 10.1073/pnas.1009843107
• Publication Date: 2010-09-14T03:02:19Z
• Authors: Peter Van Loo; Silje H. Nordgard; Ole Christian Lin...; Hege G. Russnes; Inga H. Rye; Wei Sun; Victor J. Weigman; Peter Marynen; Anders Zetterberg; Bjørn Naume; Charles M. Perou; Anne-Lise Børrese...; Vessela N. Kriste...
• Keywords: Copy number analysis; Breast carcinoma; Gene dosage

We present an allele-specific copy number analysis of the in vivo breast cancer genome. describe a unique bioinformatics approach, ASCAT (allele-specific tumors), to accurately dissect solid tumors, simultaneously estimating and adjusting for both tumor ploidy nonaberrant cell admixture. This allows calculation “ASCAT profiles” (genome-wide copy-number profiles) from which gains, losses, number-neutral events, loss heterozygosity (LOH) can be determined. In early-stage carcinoma series, we observe aneuploidy (>2.7n) 45% cases average admixture 49%. By aggregation profiles across our obtain genomic frequency distributions gains as well genome-wide views LOH events cancer. addition, reveal differences aberrant fraction, ploidy, LOH, between five previously identified molecular subtypes. Basal-like carcinomas have significantly higher compared with other subtypes, their show large-scale material during development, followed by whole-genome duplication, resulting near-triploid genomes. Finally, profiles, construct map allelic skewness cancer, indicating loci where one allele is preferentially lost, whereas gained. hypothesize that these alternative alleles different influence on development.