{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T22:53:40Z","timestamp":1790463220974,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2010,6,2]],"date-time":"2010-06-02T00:00:00Z","timestamp":1275436800000},"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":[[2010,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Survival of the malignant Hodgkin and Reed\/Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL) is dependent on constitutive activation of the nuclear factor \u03baB (NF\u2010\u03baB) transcription factor. The deubiquitinating enzyme CYLD is a negative regulator of NF\u2010\u03baB and known to function as a tumor suppressor. To determine whether <jats:italic>CYLD<\/jats:italic> mutations play a role in cHL pathogenesis, we sequenced the gene in cHL cell lines and microdissected HRS cells obtained from lymph\u2010node biopsies. A biallelic inactivation by mutations was found in the cHL cell\u2010line KM\u2010H2. However, the other seven cHL cell lines analyzed and HRS cells of 10 primary cHL cases did not show any mutations. By interphase cytogenetics, a (sub)clonal biallelic <jats:italic>CYLD<\/jats:italic> deletion was observed by interphase cytogenetics in 1 of 29 primary cHL, whereas signal patterns indicating decreased <jats:italic>CYLD<\/jats:italic> copy numbers were observed in a total of 10 of 29 primary cases. Our results suggest that biallelic <jats:italic>CYLD<\/jats:italic> mutations are rarely involved in cHL pathogenesis. Nevertheless, it is remarkable that KM\u2010H2 cells, besides the <jats:italic>CYLD<\/jats:italic> mutations, also carry inactivating mutations in the genes of two other NF\u2010\u03baB inhibitors, that is, <jats:italic>NFKBIA<\/jats:italic> and <jats:italic>TNFAIP3<\/jats:italic>, exemplifying that multiple lesions in regulators of this signaling pathway can likely cooperatively contribute to the strong NF\u2010\u03baB activity of these cells. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/gcc.20789","type":"journal-article","created":{"date-parts":[[2010,6,2]],"date-time":"2010-06-02T17:58:16Z","timestamp":1275501496000},"page":"803-809","source":"Crossref","is-referenced-by-count":44,"title":["Rare occurrence of biallelic <i>CYLD<\/i> gene mutations in classical Hodgkin 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