Abstract

Clinical testing using various array comparative genomic hybridization platforms is being incorporated rapidly into cytogenetic testing algorithms. Comprehensive validation of these complex assays presents unique challenges and very few studies reporting the validation of commercially available array platforms have been published. Sixty-seven patients with previously defined subtelomere abnormalities, representing deletions and/or duplications of all 41 clinically relevant sites, were tested in a blinded study using the Spectral Genomics Constitutional Chip 3.0. Overall, 72 of 74 (97%) subtelomeric abnormalities were concordant with previous cytogenetic studies. However, two false-negative results were documented, and issues with mismapped and suboptimal clone performance were identified that may result in failure to detect 6q and 20q subtelomeric abnormalities. The results of this study indicate that comprehensive validation is necessary before implementation of array comparative genomic hybridization platforms into a clinical setting. Specific suggestions for validation are discussed in the context of the recently proposed American College of Medical Genetics guidelines for microarray analysis for constitutional cytogenetic abnormalities.