Advances in cancer research have greatly benefited from high resolution copy number (CN) measurements provided by oligo array Comparative Genomic Hybridization (aCGH). The addition of single nucleotide polymorphism (SNP) measurements to CGH microarrays enables the detection of copy-neutral loss of heterozygosity (cnLOH) events and allelic imbalances arising from genomic instability during cancer development and progression. Nonetheless, cancer studies face challenges associated with genomes’ aneuploidy, polyclonality and mosaicism due to the admixtures of tumor and normal cells. In the quest to decipher tumor complexity, the power and sensitivity of Agilent's CGH+SNP platform has been expanded with new computational methods capable of determining clonal fraction, total CN and allele-specific CN in aneuploid samples. Genomic DNA from hematology-oncology samples, cell lines and a genotyped control sample was digested with AluI and RsaI restriction endonucleases to allow for SNP profiling at the enzymes’ restriction sites. Experimental and reference samples were differentially labeled and hybridized to the Agilent Cancer CGH+SNP microarray, containing ∼20K cancer associated CGH probes, ∼100K backbone probes and ∼60K SNP probes. The data were analyzed using algorithms with extended capability to determine clonal fraction, total and allele-specific CN of the aberrant clone. As expected, significant diversity was found in different chronic lymphocytic leukemia (CLL) tumors. In one CLL sample a small homozygous deletion and cnLOH were identified on chromosome 13. In another CLL case a trisomy of the entire chromosome 12 was observed, together with a small hemizygous deletion and cnLOH on chromosome 18. An Acute Lymphoblastic Leukemia (ALL) tumor sample was found to harbor an amplification on chromosome 6, as well as two small amplifications on chromosome X. To assess the ability of detecting low level mosaicism, we conducted a mixed sample experiment whereby a sample with a known aberration was mixed at known ratios with a matched sample not containing the aberration. The computed clonal fraction, total and allele-specific CN matched the expected values. We have shown that the new algorithms developed for cancer sample analysis determined the genotypes, total copy numbers and clonal fractions in aneuploid samples highly mixed with normal cell populations.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5095. doi:1538-7445.AM2012-5095