title: Integration of microarray analysis into the clinical diagnosis of hematological malignancies: How much can we improve cytogenetic testing?
abstract: OBJECTIVE
  To evaluate the clinical utility, diagnostic yield and rationale of integrating microarray analysis in the clinical diagnosis of hematological malignancies in comparison with classical chromosome karyotyping/fluorescence in situ hybridization (FISH).
  
  
  METHODS
  G-banded chromosome analysis, FISH and microarray studies using customized CGH and CGH+SNP designs were performed on 27 samples from patients with hematological malignancies. A comprehensive comparison of the results obtained by three methods was conducted to evaluate benefits and limitations of these techniques for clinical diagnosis.
  
  
  RESULTS
  Overall, 89.7% of chromosomal abnormalities identified by karyotyping/FISH studies were also detectable by microarray. Among 183 acquired copy number alterations (CNAs) identified by microarray, 94 were additional findings revealed in 14 cases (52%), and at least 30% of CNAs were in genomic regions of diagnostic/prognostic significance. Approximately 30% of novel alterations detected by microarray were >20 Mb in size. Balanced abnormalities were not detected by microarray; however, of the 19 apparently "balanced" rearrangements, 55% (6/11) of recurrent and 13% (1/8) of non-recurrent translocations had alterations at the breakpoints discovered by microarray.
  
  
  CONCLUSIONS
  Microarray technology enables accurate, cost-effective and time-efficient whole-genome analysis at a resolution significantly higher than that of conventional karyotyping and FISH. Array-CGH showed advantage in identification of cryptic imbalances and detection of clonal aberrations in population of non-dividing cancer cells and samples with poor chromosome morphology. The integration of microarray analysis into the cytogenetic diagnosis of hematologic malignancies has the potential to improve patient management by providing clinicians with additional disease specific and potentially clinically actionable genomic alterations.
authors: Pittsburgh Cytogenetics Laboratory, Center for Medical Genetics and Genomics, Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA.|Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA.|Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors: Jess F
authors: JF
authors: Peterson
authors: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors: Nidhi
authors: N
authors: Aggarwal
authors: Department of Medicine, Division of Hematology, University of Colorado, Denver, CO.
authors: Clayton A
authors: CA
authors: Smith
authors: Pittsburgh Cytogenetics Laboratory, Center for Medical Genetics and Genomics, Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA.|Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA.|Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors: Susanne M
authors: SM
authors: Gollin
authors: Pittsburgh Cytogenetics Laboratory, Center for Medical Genetics and Genomics, Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA.|Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA.|Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors: Urvashi
authors: U
authors: Surti
authors: Pittsburgh Cytogenetics Laboratory, Center for Medical Genetics and Genomics, Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA.|Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA.|Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.|Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors: Aleksandar
authors: A
authors: Rajkovic
authors: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors: Steven H
authors: SH
authors: Swerdlow
authors: Pittsburgh Cytogenetics Laboratory, Center for Medical Genetics and Genomics, Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA.|Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.|Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors: Svetlana A
authors: SA
authors: Yatsenko
mesh_terms: D002869:Chromosome Aberrations; D002871:Chromosome Banding / Q000379:methods; D055028:Comparative Genomic Hybridization / Q000379:methods; D020732:Cytogenetic Analysis / Q000379:methods* / Q000592:standards; D056915:DNA Copy Number Variations; D019337:Hematologic Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007621:Karyotyping / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D014178:Translocation, Genetic
keywords: Chromosome Section; array CGH; diagnosis; hematological malignancies; microarray