title: A multicenter, cross-platform clinical validation study of cancer cytogenomic arrays.
abstract: Cytogenomic microarray analysis (CMA) offers high resolution, genome-wide copy number information and is widely used in clinical laboratories for diagnosis of constitutional abnormalities. The Cancer Genomics Consortium (CGC) conducted a multiplatform, multicenter clinical validation project to compare the reliability and inter- and intralaboratory reproducibility of this technology for clinical oncology applications. Four specimen types were processed on three different microarray platforms-from Affymetrix, Agilent, and Illumina. Each microarray platform was employed at two independent test sites. The results were compared in a blinded manner with current standard methods, including karyotype, FISH, or morphology. Twenty-nine chronic lymphocytic leukemia blood, 34 myelodysplastic syndrome bone marrow, and 30 fresh frozen renal epithelial tumor samples were assessed by all six laboratories. Thirty formalin fixed paraffin embedded renal tumor samples were analyzed at the Affymetrix and Agilent test sites only. All study samples were initial diagnostic samples. Array data were analyzed at each participating site and were submitted to caArray for central analysis. Laboratory interpretive results were submitted to the central analysis team for comparison with the standard-of-care assays and for calculation of intraplatform reproducibility and cross-platform concordance. The results demonstrated that the three microarray platforms 1) detect clinically actionable genomic changes in cancer compatible to standard-of-care methods; 2) further define cytogenetic aberrations; 3) identify submicroscopic alterations and loss of heterozygosity (LOH); and 4) yield consistent results within and between laboratories. Based on this study, the CGC concludes that CMA is a sensitive and reliable technique for copy number and LOH assessment that may be used for clinical oncology genomic analysis.
authors.affiliation: Baylor College of Medicine, Houston, TX, USA. Electronic address: marilynli05@gmail.com.
authors.forename: Marilyn M
authors.initials: MM
authors.lastname: Li
authors.affiliation: Baylor College of Medicine, Houston, TX, USA.
authors.forename: Federico A
authors.initials: FA
authors.lastname: Monzon
authors.affiliation: The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Jaclyn A
authors.initials: JA
authors.lastname: Biegel
authors.affiliation: Columbia University, New York, NY.
authors.forename: Vaidehi
authors.initials: V
authors.lastname: Jobanputra
authors.affiliation: University of Wisconsin, Madison, WI, USA.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Laffin
authors.affiliation: Columbia University, New York, NY.
authors.forename: Brynn
authors.initials: B
authors.lastname: Levy
authors.affiliation: GenPath, Bioreference Laboratories, Elmwood Park, NJ, USA.
authors.forename: Annette
authors.initials: A
authors.lastname: Leon
authors.affiliation: University of Massachusetts, Worcester, MA, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Miron
authors.affiliation: Emory University, Atlanta, GA, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Rossi
authors.affiliation: Rutgers-New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA.
authors.forename: Gokce
authors.initials: G
authors.lastname: Toruner
authors.affiliation: Baylor College of Medicine, Houston, TX, USA.
authors.forename: Karla
authors.initials: K
authors.lastname: Alvarez
authors.affiliation: Emory University, Atlanta, GA, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Doho
authors.affiliation: The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Dougherty
authors.affiliation: Baylor College of Medicine, Houston, TX, USA.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Hu
authors.affiliation: Creighton University, Omaha, NE, USA.
authors.forename: Shera
authors.initials: S
authors.lastname: Kash
authors.affiliation: Rutgers-New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA.
authors.forename: Deanna
authors.initials: D
authors.lastname: Streck
authors.affiliation: Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Iya
authors.initials: I
authors.lastname: Znoyko
authors.affiliation: Creighton University, Omaha, NE, USA.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Hagenkord
authors.affiliation: Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Daynna J
authors.initials: DJ
authors.lastname: Wolff
mesh_terms: D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization / Q000379:methods*; D020732:Cytogenetic Analysis / Q000379:methods*; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D059785:Karyotype; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000235:genetics; D019656:Loss of Heterozygosity; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000235:genetics; D009369:Neoplasms / Q000175:diagnosis* / Q000235:genetics; D009375:Neoplasms, Glandular and Epithelial / Q000175:diagnosis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D015203:Reproducibility of Results; D059039:Standard of Care
keywords: Cancer Genomics Consortium; Cancer cytogenomic microarray; Chronic lymphocytic leukemia; Myelodysplastic syndrome; Renal epithelial tumor