{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T22:49:15Z","timestamp":1785883755711,"version":"3.56.0"},"reference-count":52,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2011,8,30]],"date-time":"2011-08-30T00:00:00Z","timestamp":1314662400000},"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;amp; Cancer"],"published-print":{"date-parts":[[2011,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hodgkin\/Reed\u2013Sternberg (HRS) cells represent the malignant fraction of infiltrated lymph nodes in Hodgkin lymphoma (HL). Although HRS cells display multiple chromosomal aberrations, few are recurrent and the targeted genes unknown. However, understanding the pathology of HL and developing rational therapies may well require identifying putative deregulated genes. Here, we analyzed the karyotype of the well\u2010defined HL cell line L\u20101236 by spectral karyotyping and identified multiple abnormalities, therein, notably t(4;8)(q27;q24) which includes two breakpoint regions previously highlighted in HL. Target genes at 4q27 and 8q24 were shortlisted by high density genomic arrays and fluorescence in situ hybridization. Expression analysis of candidate target genes revealed conspicuous activation of phosphodiesterase <jats:italic>PDE5A<\/jats:italic> at 4q27 and inhibition of homeobox gene <jats:italic>ZHX2<\/jats:italic> at 8q24. Treatment of L\u20101236 with PDE5A\u2010inhibitor sildenafil or with siRNA directed against <jats:italic>PDE5A<\/jats:italic> and concomitant stimulation with cyclic guanosine monophosphate (cGMP) resulted in enhanced apoptosis, indicating <jats:italic>PDE5A<\/jats:italic> as an oncogene. Expression profiling of L\u20101236 cells following siRNA\u2010mediated knockdown of <jats:italic>ZHX2<\/jats:italic> showed inhibition of genes regulating differentiation and apoptosis, suggesting tumor suppressor activity of <jats:italic>ZHX2<\/jats:italic>. Downstream genes included <jats:italic>STAT1<\/jats:italic> and several STAT1\u2010target genes, indicating activation of STAT1\u2010signaling by <jats:italic>ZHX2<\/jats:italic> as analyzed by RQ\u2010PCR and western blot. Taken together, we have identified a novel aberration with recurrent breakpoints in HL, t(4;8)(q27;q24), which activate <jats:italic>PDE5A<\/jats:italic> and repress <jats:italic>ZHX2<\/jats:italic>, deregulating apoptosis, differentiation, and STAT1\u2010signaling in HL cells. \u00a9 2011 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/gcc.20920","type":"journal-article","created":{"date-parts":[[2011,9,1]],"date-time":"2011-09-01T05:46:21Z","timestamp":1314855981000},"page":"996-1009","source":"Crossref","is-referenced-by-count":33,"title":["t(4;8)(q27;q24) in Hodgkin lymphoma cells targets phosphodiesterase <i>PDE5A<\/i> and homeobox gene <i>ZHX2<\/i>"],"prefix":"10.1002","volume":"50","author":[{"given":"Stefan","family":"Nagel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Rosenwald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinna","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maren","family":"Kaufmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans G.","family":"Drexler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roderick A. 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