title: The potential of copy number gains and losses, detected by array-based comparative genomic hybridization, for computational differential diagnosis of B-cell lymphomas and genetic regions involved in lymphomagenesis.
abstract: BACKGROUND
  The differentiation of biologically and clinically different malignant lymphoma diseases or subtypes is crucial because it leads to better prognostication and therapeutic decision-making. Attempts have been made at subtype classification for diagnosing lymphomas on the basis of gene-expression profiling. Although array-based comparative genomic hybridization (array CGH) has identified a characteristic genomic alteration pattern for each disease entity, it has not been clear whether each patient with certain genomic alterations can be classified by array CGH data.
  
  
  METHODS
  Data on copy number gains and losses for 46 diffuse large B-cell lymphomas and 29 mantle cell lymphomas were used. The gene expressions of the diffuse large B-cell lymphomas cases were profiled and hierarchical clustering revealed that 28 of them were of the activated B-cell type and 18 were of the germinal center-B-cell type. Using these data, we developed a computer algorithm to classify lymphoma diseases or subtypes on the basis of copy number gains and losses.
  
  
  RESULTS
  The method correctly classified 88% of the diffuse large B-cell lymphomas and mantle cell lymphomas, and 83% of the activated B-cell and germinal center-B-cell subtypes. These results demonstrate that copy number gains and losses detected by array CGH can be used for classifying lymphomas into biologically and clinically distinct diseases or subtypes.
  
  
  CONCLUSIONS
  Our computer algorithm based on array CGH data successfully classified diffuse large B-cell lymphomas and mantle cell lymphomas and activated B-cell and germinal center-B-cell subtypes with high accuracy. An important finding is that the regions automatically identified by the computer algorithm were located in the critical regions that are likely to be involved in the development of lymphoma.
authors.affiliation: Department of Scientific and Engineering Simulation, Nagoya Institute of Technology, Nagoya, Aichi, Japan. takeuchi.ichiro@nitech.ac.jp
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takeuchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tagawa
authors.forename: Akira
authors.initials: A
authors.lastname: Tsujikawa
authors.forename: Masao
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Miyuki
authors.initials: M
authors.lastname: Katayama-Suguro
authors.forename: Ying
authors.initials: Y
authors.lastname: Guo
authors.forename: Masao
authors.initials: M
authors.lastname: Seto
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D003201:Computers; D003937:Diagnosis, Differential; D018628:Gene Dosage / Q000235:genetics*; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000145:classification / Q000175:diagnosis* / Q000235:genetics*; D020522:Lymphoma, Mantle-Cell / Q000145:classification / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis