Deregulation of COMMD1 Is Associated with Poor Prognosis in Diffuse Large B-cell Lymphoma

• Published in: PloS one Vol. 9; no. 3; p. e91031
• Main Authors: Taskinen, Minna, Louhimo, Riku, Koivula, Satu, Chen, Ping, Rantanen, Ville, Holte, Harald, Delabie, Jan, Karjalainen-Lindsberg, Marja-Liisa, Björkholm, Magnus, Fluge, Øystein, Pedersen, Lars Møller, Fjordén, Karin, Jerkeman, Mats, Eriksson, Mikael, Hautaniemi, Sampsa, Leppä, Sirpa
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13.03.2014; Public Library of Science (PLoS)
• Subjects: Aberration; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Adult; Aged; Analysis; B-cell lymphoma; Biology; Cancer; Cancer and Oncology; Cancer och onkologi; Cell cycle; Cell survival; Central nervous system; Chemotherapy; Chromosomes; Clinical Medicine; Combined Modality Therapy; Comparative Genomic Hybridization; Copy number; Cytogenetics; Deregulation; DNA microarrays; Ethics; Female; Gene expression; Gene Expression Regulation, Neoplastic; Genes; Genetic Predisposition to Disease; Genomes; Hematology; Hospitals; Humans; Hybridization; Immunohistochemistry; Immunotherapy; Impact analysis; Klinisk medicin; Lymphocytes B; Lymphoma; Lymphoma, Large B-Cell, Diffuse - diagnosis; Lymphoma, Large B-Cell, Diffuse - drug therapy; Lymphoma, Large B-Cell, Diffuse - genetics; Lymphoma, Large B-Cell, Diffuse - metabolism; Lymphomas; Male; Medical and Health Sciences; Medical prognosis; Medical research; Medicin och hälsovetenskap; Medicine; Middle Aged; Oligonucleotide Array Sequence Analysis; Oncology; Patients; Prognosis; Prophylaxis; Prospective Studies; Survival; Treatment Outcome; Treatment resistance; Tumors; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0091031

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. 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. 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. 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. ClinicalTrials.gov NCT01502982.