The costimulatory molecule CD70 is regulated by distinct molecular mechanisms and is associated with overall survival in diffuse large B‐cell lymphoma

<jats:p>In diffuse large B‐cell lymphomas (DLBCL), a recurrent deletion of the 19p13 region has recently been described.<jats:italic>CD70</jats:italic>and<jats:italic>TNFSF9</jats:italic>genes are suspected tumor suppressor genes, but previous studies suggest an oncogenic role for<jats:italic>CD70</jats:italic>. Therefore, we studied the consequences of variation in<jats:italic>CD70</jats:italic>copy number and epigenetic modifications on<jats:italic>CD70</jats:italic>expression. Copy‐number variation was investigated in 144<jats:italic>de novo</jats:italic>DLBCL tissues by comparative genomic hybridization array and quantitative multiplex PCR. Gene expression was assessed by quantitative RT‐PCR, and<jats:italic>CD70</jats:italic>promoter methylation was determined by pyrosequencing. The 19p13.3.2 region was deleted in 21 (14.6%) cases, which allowed the minimal commonly deleted region of 57 Kb that exclusively includes the<jats:italic>CD70</jats:italic>gene to be defined. Homozygous deletions were observed in four (2.7%) cases, and acquired single‐nucleotide variations of<jats:italic>CD70</jats:italic>were detected in nine (6.3%) cases.<jats:italic>CD70</jats:italic>was highly expressed in both germinal centre B‐cell‐like (GCB) and activated B‐cell‐like (ABC) DLBCL compared to normal tissue, with distinct molecular mechanisms of mRNA expression regulation. A gene dosage effect was observed in the GCB subtype, whereas promoter methylation was the predominant mechanism of down regulation in the ABC subtype. However, high<jats:italic>CD70</jats:italic>expression levels correlated to shorter overall survival in both the GCB (<jats:italic>P</jats:italic>= 0.0021) and the ABC (<jats:italic>P</jats:italic>=0.0158) subtypes. In conclusion,<jats:italic>CD70</jats:italic>is targeted by recurrent deletions, somatic mutations and promoter hypermethylation, but its high level of expression is related to an unfavorable outcome, indicating that this molecule may constitute a potential therapeutic target in selected DLBCL. © 2013 Wiley Periodicals, Inc.</jats:p>