{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T07:31:36Z","timestamp":1791185496942,"version":"4.1.0"},"reference-count":69,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2013,5,28]],"date-time":"2013-05-28T00:00:00Z","timestamp":1369699200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2013,8]]},"abstract":"<jats:p>In diffuse large B\u2010cell 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\u2010number 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\u2010PCR, 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\u2010nucleotide 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\u2010cell\u2010like (GCB) and activated B\u2010cell\u2010like (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. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/gcc.22072","type":"journal-article","created":{"date-parts":[[2013,5,28]],"date-time":"2013-05-28T10:10:42Z","timestamp":1369735842000},"page":"764-774","source":"Crossref","is-referenced-by-count":45,"title":["The costimulatory molecule CD70 is regulated by distinct molecular mechanisms and is associated with overall survival in diffuse large B\u2010cell lymphoma"],"prefix":"10.1002","volume":"52","author":[{"given":"P.","family":"Bertrand","sequence":"first","affiliation":[{"name":"Department of Hematology IRIB, and Centre Henri Becquerel, INSERM, U918 and Normandie University Rouen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Maingonnat","sequence":"additional","affiliation":[{"name":"Department of Hematology IRIB, and Centre Henri Becquerel, INSERM, U918 and Normandie University Rouen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Penther","sequence":"additional","affiliation":[{"name":"Department of Hematology IRIB, and Centre Henri Becquerel, INSERM, U918 and Normandie University Rouen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Guney","sequence":"additional","affiliation":[{"name":"Department of Hematology IRIB, and Centre Henri Becquerel, INSERM, U918 and Normandie University Rouen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Ruminy","sequence":"additional","affiliation":[{"name":"Department of Hematology IRIB, and Centre Henri Becquerel, INSERM, U918 and Normandie University Rouen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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