title: Reproducibility and performance of virtual karyotyping with SNP microarrays for the detection of chromosomal imbalances in formalin-fixed paraffin-embedded tissues.
abstract: BACKGROUND
  Chromosomal imbalances are commonly seen in cancer and inherited genetic diseases. These imbalances may assist in the diagnosis, prognosis, and/or therapeutic management of certain neoplasms. Several methods for detecting chromosomal imbalances, such as, fluorescent in situ hybridization, array comparative genomic hybridization, and single nucleotide polymorphism (SNP) arrays have proven useful in formalin-fixed paraffin-embedded (FFPE) tissues. Here, we report the performance and reproducibility of virtual karyotyping of FFPE tissues with Affymetrix SNP arrays.
  
  
  METHODS
  Virtual karyotypes from 442 FFPE tumor samples were generated using the Affymetrix GeneChip Mapping 10K Xba 2.0 and/or 250K Nsp SNP mapping arrays. Samples ranged from a few weeks to 17 years in archival storage. Virtual karyotypes were assessed for copy number changes, loss of heterozygosity, and acquired uniparental disomy.
  
  
  RESULTS
  Overall, 75.3% of samples produced interpretable virtual karyotypes with the 10K arrays and 76.7% in the 250K arrays. Parameters for the selection of samples for hybridization were determined, which increased the success rate in both platforms to 81.3 and 92.6%, respectively. FFPE virtual karyotypes generated with both 10K Xba 2.0 and 250K Nsp arrays showed 100% concordance in intralaboratory and interlaboratory reproducibility studies. Samples older than 7 years showed decreased performance.
  
  
  CONCLUSIONS
  SNP arrays are a reliable, reproducible, and robust platform for the virtual karyotyping of FFPE tumor tissues with performance characteristics adequate for clinical application. Parameters that most significantly affected sample performance were sample age and storage conditions.
authors.affiliation: Department of Pathology, The Methodist Hospital and The Methodist Hospital Research Institute, Houston, TX, USA.
authors.forename: Karla
authors.initials: K
authors.lastname: Alvarez
authors.forename: Shera F
authors.initials: SF
authors.lastname: Kash
authors.forename: Maureen A
authors.initials: MA
authors.lastname: Lyons-Weiler
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Leif E
authors.initials: LE
authors.lastname: Peterson
authors.forename: Benita
authors.initials: B
authors.lastname: Mathai
authors.forename: Jill M
authors.initials: JM
authors.lastname: Hagenkord
authors.forename: Federico A
authors.initials: FA
authors.lastname: Monzon
mesh_terms: D000293:Adolescent; D000782:Aneuploidy; D002648:Child; D002675:Child, Preschool; D005404:Fixatives / Q000494:pharmacology; D005557:Formaldehyde / Q000494:pharmacology; D006801:Humans; D007223:Infant; D007621:Karyotyping / Q000379:methods; D046228:Microarray Analysis / Q000379:methods*; D009369:Neoplasms / Q000175:diagnosis* / Q000473:pathology*; D016612:Paraffin Embedding; D057089:Pathology, Molecular / Q000379:methods*; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D013048:Specimen Handling / Q000379:methods*; D014021:Tissue Preservation
chemical_list: D005404:Fixatives; D005557:Formaldehyde