Abstract 4655: Molecular Inversion Probe analysis using OncoScan™ FFPE Assay Kit to detect copy number aberrations and somatic mutations in lung tumor DNA samples from formalin-fixed paraffin-embedded (FFPE) tissue

DNA copy number (CN) studies hold great promise for the discovery of clinical biomarkers to predict disease course, recurrence risk, and response to therapy. The molecular characterization of a tumor genome across many samples helps to classify cancers in a biologically and clinically relevant manner. While exciting results have been found with genes already known to be involved in key pathways, confirming early results and genome-wide testing requires large numbers of well-characterized clinical samples. A vast collection of hundreds of millions of stored FFPE samples already exists. Unfortunately, many genomic assays fail to produce high-quality CN and genotype data from FFPE samples, given the degradation and chemical changes to the DNA and the small quantity obtained from tiny tissue samples. The higher rate of sequencing artifacts and genotyping failures in FFPE samples restricts the application of these promising whole-genome scanning technologies to the limited number of fresh-frozen samples. OncoScan™ FFPE Assay Kit is designed to interrogate the whole genome for copy number aberrations (CNAs), loss of heterozygosity (LOH), and selected somatic mutations (SMs) and captures the alleles of over 220,000 SNPs at carefully selected genomic locations. These SNPs are evenly distributed across the genome and with increased density within ∼900 cancer-related genes. Based on Molecular Inversion Probe (MIP) technology, several OncoScan Assay Kit features make it highly suitable for the analysis of FFPE tissue-derived DNA. The assay uses only 80 ng input DNA with no requirement for amplification of the genomic DNA; rather, the probe itself is amplified, leading to a high signal-to-noise ratio. The entire assay can be run such that results can be obtained within 48 hours of gDNA extraction. Cancer sample data are complex because each sample is inherently mosaic, comprised of a mixture of normal cells along with one or multiple tumor clones. OncoScan FFPE Assay Kit includes a component algorithm that specifically addresses the issue of normal contamination in the tumor sample. In this study, we will describe the characterization of genomic variations in a set of 67 lung tumor samples collected in collaboration with Cancer Research UK (CRUK). From each sample, 80 ng FFPE gDNA has been extracted and purified as input to OncoScan Assay Kit. Collectively, the tumor genomes showed frequent CN gains on chromosomes 1q, 5p, 6p, 7, 8q, and 17q and frequent CN losses on chromosomes 6q and 17p. The number of structural aberrations per sample ranged from 3 to 340, with an average of 94. The assay simultaneously interrogates 74 SMs of interest using a panel of 64 MIPs. Forty-nine samples had at least 1 SM call (1 sample having a maximum of 4). Citation Format: Ron Sapolsky, Anju Shukla, Sumathi Venkatapathy, Chuan Chen, Carsten Bruckner, Vicky Huynh, Liansen Liu, Xuan Shen, Kent Suyenaga, Patrick Weaver, Wai Wu, Bitao Liu, Matt Ghent, Benjamin Bolstad, Farooq Siddiqui, Diana Abdueva, Mirjana Alvi, Eric Fung, Jeanette Schmidt, Lawrence Greenfield. Molecular Inversion Probe analysis using OncoScan™ FFPE Assay Kit to detect copy number aberrations and somatic mutations in lung tumor DNA samples from formalin-fixed paraffin-embedded (FFPE) tissue. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4655. doi:10.1158/1538-7445.AM2014-4655