Abstract 5075: Genome-wide analysis of DNA copy number variations in osteosarcoma

Abstract

Abstract Objectives: Copy number variations (CNVs) such as deletions, amplifications and duplications across the whole genome may contribute to Osteosarcoma (OS) tumorigenesis. Detection of genomic regions containing these changes is extremely important for both the basic understanding of OS and its diagnosis. In this study we performed Whole Genome Genotyping (WGG) using high-density SNP arrays to detect CNVs in OS tumors and blood. A major advantage of this technology is the simultaneous detection of both allelic frequencies and CNVs. Methods: WGG analysis was performed using 35 high-grade intramedullary OS and 8 parosteal sarcoma tumor DNAs. 10 matching germline DNAs from blood were also included into the analysis. 250 nanograms of DNA were hybridized onto the Illumina 610 Quad BeadChips using the Infinium II WGG assay. The WGG data was analysed using Bead Studio and Partek software. Results: SNP array based Whole Genome Genotyping revealed a large number of chromosomal aberrations in OS. Preliminary analysis of 35 OS tumor DNAs showed high levels of recurrent amplification of 1p36, 3p12.1, 6q14, 12q13-15, 17p11.2, 20p12; and deletion of 3q26.31, 6p21, 6q16.3, 7q21, 7q35, 8q24.13, 9p21 and 17p13 regions. Parosteal tumor DNAs displayed a high level of amplification of the 12q13-15 amplicon. Amplification status of genes from 17p11.2 (PMP22, NCOR1, COPS3 and TOM1L2) and 12q14 (CDK4 and MDM2) was validated by Real-Time PCR. Some tumors exhibited whole chromosome arm deletions and/or duplications. Conclusions: OS tumors exhibit chromosomal alterations that can be detected using WGG. Comparison of normal and tumour DNAs from the same subjects can be used to identify CNV associated with OS development and progression. Current analyses include comparisons of CNV data and gene expression profiles of the same OS tumours to discover genes that may be biologically relevant targets in OS. 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 5075. doi:1538-7445.AM2012-5075