High-resolution array CGH increases heterogeneity tolerance in the analysis of clinical samples

• Published in: Genomics (San Diego, Calif.) Vol. 85; no. 6; pp. 790 - 793
• Main Authors: Garnis, Cathie, Coe, Bradley P., Lam, Stephen L., MacAulay, Calum, Lam, Wan L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2005
• Subjects: Array CGH; Biomarkers, Tumor - genetics; Genome, Human; Humans; Matrix CGH; Microdissection; Neoplasms - genetics; Normal cell contamination; Nucleic Acid Hybridization - methods; Sensitivity and Specificity; SMRT array; Tiling path array; Tissue heterogeneity; Microdissection; Array CGH; Tissue heterogeneity; SMRT array; Tiling path array; Matrix CGH; Normal cell contamination
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1016/j.ygeno.2005.02.015

Recent advances in array comparative genomic hybridization (array CGH) technology are revolutionizing our understanding of tumor genomes. Marker-based arrays enable rapid survey at megabase intervals, while tiling path arrays examine the entire genome in unprecedented detail. Tumor biopsies are typically small and contain infiltrating stromal cells, requiring tedious microdissection. Tissue heterogeneity is a major barrier to high-throughput profiling of tumor genomes and is also an important consideration for the introduction of array CGH to clinical settings. We propose that increasing array resolution will enhance detection sensitivity in mixed tissues and as a result significantly reduce microdissection requirements. In this study, we first simulated normal cell contamination to determine the heterogeneity tolerance of array CGH and then validated this detection sensitivity model on cancer specimens using the newly developed submegabase resolution tiling-set (SMRT) array, which spans the human genome with 32,433 overlapping BAC clones.