title: Detection of clonal evolution in hematopoietic malignancies by combining comparative genomic hybridization and single nucleotide polymorphism arrays.
abstract: BACKGROUND
  Array comparative genomic hybridization (aCGH) has become a powerful tool for analyzing hematopoietic neoplasms and identifying genome-wide copy number changes in a single assay. aCGH also has superior resolution compared with fluorescence in situ hybridization (FISH) or conventional cytogenetics. Integration of single nucleotide polymorphism (SNP) probes with microarray analysis allows additional identification of acquired uniparental disomy, a copy neutral aberration with known potential to contribute to tumor pathogenesis. However, a limitation of microarray analysis has been the inability to detect clonal heterogeneity in a sample.
  
  
  METHODS
  This study comprised 16 samples (acute myeloid leukemia, myelodysplastic syndrome, chronic lymphocytic leukemia, plasma cell neoplasm) with complex cytogenetic features and evidence of clonal evolution. We used an integrated manual peak reassignment approach combining analysis of aCGH and SNP microarray data for characterization of subclonal abnormalities. We compared array findings with results obtained from conventional cytogenetic and FISH studies.
  
  
  RESULTS
  Clonal heterogeneity was detected in 13 of 16 samples by microarray on the basis of log2 values. Use of the manual peak reassignment analysis approach improved resolution of the sample's clonal composition and genetic heterogeneity in 10 of 13 (77%) patients. Moreover, in 3 patients, clonal disease progression was revealed by array analysis that was not evident by cytogenetic or FISH studies.
  
  
  CONCLUSIONS
  Genetic abnormalities originating from separate clonal subpopulations can be identified and further characterized by combining aCGH and SNP hybridization results from 1 integrated microarray chip by use of the manual peak reassignment technique. Its clinical utility in comparison to conventional cytogenetic or FISH studies is demonstrated.
authors.affiliation: HematoLogics Inc., Seattle, WA.
authors.forename: Luise
authors.initials: L
authors.lastname: Hartmann
authors.affiliation: HematoLogics Inc., Seattle, WA.
authors.forename: Christine F
authors.initials: CF
authors.lastname: Stephenson
authors.affiliation: HematoLogics Inc., Seattle, WA.
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Verkamp
authors.affiliation: HematoLogics Inc., Seattle, WA.
authors.forename: Krystal R
authors.initials: KR
authors.lastname: Johnson
authors.affiliation: HematoLogics Inc., Seattle, WA.
authors.forename: Bettina
authors.initials: B
authors.lastname: Burnworth
authors.affiliation: HematoLogics Inc., Seattle, WA.
authors.forename: Kelle
authors.initials: K
authors.lastname: Hammock
authors.affiliation: HematoLogics Inc., Seattle, WA.
authors.forename: Lisa Eidenschink
authors.initials: LE
authors.lastname: Brodersen
authors.affiliation: HematoLogics Inc., Seattle, WA.
authors.forename: Monica E
authors.initials: ME
authors.lastname: de Baca
authors.affiliation: HematoLogics Inc., Seattle, WA.
authors.forename: Denise A
authors.initials: DA
authors.lastname: Wells
authors.affiliation: HematoLogics Inc., Seattle, WA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Loken
authors.affiliation: HematoLogics Inc., Seattle, WA. barbara@hematologics.com.
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Zehentner
mesh_terms: D060965:Clonal Evolution / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D019337:Hematologic Neoplasms / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*