title: Cross-laboratory validation of the OncoScan® FFPE Assay, a multiplex tool for whole genome tumour profiling.
abstract: BACKGROUND
  Adoption of new technology in both basic research and clinical settings requires rigorous validation of analytical performance. The OncoScan® FFPE Assay is a multiplexing tool that offers genome-wide copy number and loss of heterozygosity detection, as well as identification of frequently tested somatic mutations.
  
  
  METHODS
  In this study, 162 formalin fixed paraffin embedded samples, representing six different tumour types, were profiled in triplicate across three independent laboratories. OncoScan® formalin fixed paraffin embedded assay data was then analysed for reproducibility of genome-wide copy number, loss of heterozygosity and somatic mutations. Where available, somatic mutation data was compared to data from orthogonal technologies (pyro/sanger sequencing).
  
  
  RESULTS
  Cross site comparisons of genome-wide copy number and loss of heterozygosity profiles showed greater than 95% average agreement between sites. Somatic mutations pre-validated by orthogonal technologies showed greater than 90% agreement with OncoScan® somatic mutation calls and somatic mutation concordance between sites averaged 97%.
  
  
  CONCLUSIONS
  Reproducibility of whole-genome copy number, loss of heterozygosity and somatic mutation data using the OncoScan® assay has been demonstrated with comparatively low DNA inputs from a range of highly degraded formalin fixed paraffin embedded samples. In addition, our data shows examples of clinically-relevant aberrations that demonstrate the potential utility of the OncoScan® assay as a robust clinical tool for guiding tumour therapy.
authors.affiliation: Affymetrix UK Ltd, High Wycombe, UK. Joseph_Foster@affymetrix.com.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Foster
authors.affiliation: Affymetrix UK Ltd, High Wycombe, UK. Assa_Oumie@affymetrix.com.
authors.forename: Assa
authors.initials: A
authors.lastname: Oumie
authors.affiliation: West Midlands Regional Genetics Laboratory, Birmingham, UK. Fiona.Togneri@bwnft.nhs.uk.
authors.forename: Fiona S
authors.initials: FS
authors.lastname: Togneri
authors.affiliation: West Midlands Regional Genetics Laboratory, Birmingham, UK. Fabiana.RamosVasques@bwnft.nhs.uk.
authors.forename: Fabiana Ramos
authors.initials: FR
authors.lastname: Vasques
authors.affiliation: West Midlands Regional Genetics Laboratory, Birmingham, UK. debra.hau@hotmail.co.uk.
authors.forename: Debra
authors.initials: D
authors.lastname: Hau
authors.affiliation: Leeds Institute of Cancer and Pathology, Section of Tumour Biology and Pathology, Leeds University, Leeds, UK. medmta@leeds.ac.uk.
authors.forename: Morag
authors.initials: M
authors.lastname: Taylor
authors.affiliation: Leeds Institute of Cancer and Pathology, Section of Tumour Biology and Pathology, Leeds University, Leeds, UK. e.tinkler@leeds.ac.uk.
authors.forename: Emma
authors.initials: E
authors.lastname: Tinkler-Hundal
authors.affiliation: Leeds Institute of Cancer and Pathology, Section of Tumour Biology and Pathology, Leeds University, Leeds, UK. K.Southward@leeds.ac.uk.
authors.forename: Katie
authors.initials: K
authors.lastname: Southward
authors.affiliation: Almac Diagnostics, Craigavon, Northern Ireland, UK. paul.medlow@almacgroup.com.
authors.forename: Paul
authors.initials: P
authors.lastname: Medlow
authors.affiliation: Almac Diagnostics, Craigavon, Northern Ireland, UK. keith.crosby@almacgroup.com.
authors.forename: Keith
authors.initials: K
authors.lastname: McGreeghan-Crosby
authors.affiliation: Almac Diagnostics, Craigavon, Northern Ireland, UK. iris.halfpenny@almacgroup.com.
authors.forename: Iris
authors.initials: I
authors.lastname: Halfpenny
authors.affiliation: West Midlands Regional Genetics Laboratory, Birmingham, UK. Dominic.McMullan@bwnft.nhs.uk.
authors.forename: Dominic J
authors.initials: DJ
authors.lastname: McMullan
authors.affiliation: Leeds Institute of Cancer and Pathology, Section of Tumour Biology and Pathology, Leeds University, Leeds, UK. P.Quirke@leeds.ac.uk.
authors.forename: Phil
authors.initials: P
authors.lastname: Quirke
authors.affiliation: Almac Diagnostics, Craigavon, Northern Ireland, UK. karen.keating@almacgroup.com.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Keating
authors.affiliation: West Midlands Regional Genetics Laboratory, Birmingham, UK. Mike.Griffiths@bwnft.nhs.uk.
authors.forename: Mike
authors.initials: M
authors.lastname: Griffiths
authors.affiliation: Affymetrix UK Ltd, High Wycombe, UK. Karen_Spink@affymetrix.com.
authors.forename: Karen G
authors.initials: KG
authors.lastname: Spink
authors.affiliation: Affymetrix UK Ltd, High Wycombe, UK. Fiona_Brew@affymetrix.com.
authors.forename: Fiona
authors.initials: F
authors.lastname: Brew
mesh_terms: D019411:Clinical Laboratory Techniques / Q000592:standards*; D004252:DNA Mutational Analysis; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D016612:Paraffin Embedding; D011786:Quality Control; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA; D016707:Tissue Fixation / Q000379:methods*