title: Deregulation of COMMD1 is associated with poor prognosis in diffuse large B-cell lymphoma.
abstract: BACKGROUND
  Despite improved survival for the patients with diffuse large B-cell lymphoma (DLBCL), the prognosis after relapse is poor. The aim was to identify molecular events that contribute to relapse and treatment resistance in DLBCL.
  
  
  METHODS
  We analysed 51 prospectively collected pretreatment tumour samples from clinically high risk patients treated in a Nordic phase II study with dose-dense chemoimmunotherapy and central nervous system prophylaxis with high resolution array comparative genomic hybridization (aCGH) and gene expression microarrays. Major finding was validated at the protein level immunohistochemically in a trial specific tissue microarray series of 70, and in an independent validation series of 146 patients.
  
  
  RESULTS
  We identified 31 genes whose expression changes were strongly associated with copy number aberrations. In addition, gains of chromosomes 2p15 and 18q12.2 were associated with unfavourable survival. The 2p15 aberration harboured COMMD1 gene, whose expression had a significant adverse prognostic impact on survival. Immunohistochemical analysis of COMMD1 expression in two series confirmed the association of COMMD1 expression with poor prognosis.
  
  
  CONCLUSIONS
  COMMD1 is a potential novel prognostic factor in DLBCLs. The results highlight the value of integrated comprehensive analysis to identify prognostic markers and genetic driver events not previously implicated in DLBCL.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01502982.
authors.affiliation: Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland; Genome Scale Biology Program, University of Helsinki, Helsinki, Finland.
authors.forename: Minna
authors.initials: M
authors.lastname: Taskinen
authors.affiliation: Genome Scale Biology Program, University of Helsinki, Helsinki, Finland.
authors.forename: Riku
authors.initials: R
authors.lastname: Louhimo
authors.affiliation: Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland; Genome Scale Biology Program, University of Helsinki, Helsinki, Finland.
authors.forename: Satu
authors.initials: S
authors.lastname: Koivula
authors.affiliation: Genome Scale Biology Program, University of Helsinki, Helsinki, Finland.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.affiliation: Genome Scale Biology Program, University of Helsinki, Helsinki, Finland.
authors.forename: Ville
authors.initials: V
authors.lastname: Rantanen
authors.affiliation: Department of Oncology, Oslo University Hospital, Oslo, Norway.
authors.forename: Harald
authors.initials: H
authors.lastname: Holte
authors.affiliation: Department of Pathology, Oslo University Hospital, Oslo, Norway.
authors.forename: Jan
authors.initials: J
authors.lastname: Delabie
authors.affiliation: Department of Pathology, Haartman Institute, University of Helsinki, Helsinki, Finland.
authors.forename: Marja-Liisa
authors.initials: ML
authors.lastname: Karjalainen-Lindsberg
authors.affiliation: Department of Medicine, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Björkholm
authors.affiliation: Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway.
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Fluge
authors.affiliation: Department of Hematology, Odense University Hospital, Odense, Denmark.
authors.forename: Lars Møller
authors.initials: LM
authors.lastname: Pedersen
authors.affiliation: Department of Oncology, Lund University Hospital, Lund, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Fjordén
authors.affiliation: Department of Oncology, Lund University Hospital, Lund, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Jerkeman
authors.affiliation: Department of Oncology, Lund University Hospital, Lund, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Eriksson
authors.affiliation: Genome Scale Biology Program, University of Helsinki, Helsinki, Finland.
authors.forename: Sampsa
authors.initials: S
authors.lastname: Hautaniemi
authors.affiliation: Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland; Genome Scale Biology Program, University of Helsinki, Helsinki, Finland.
authors.forename: Sirpa
authors.initials: S
authors.lastname: Leppä
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D003131:Combined Modality Therapy; D055028:Comparative Genomic Hybridization; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D011446:Prospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C480519:COMMD1 protein, human