{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:16:25Z","timestamp":1791411385223,"version":"4.3.3"},"reference-count":28,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,10,28]],"date-time":"2005-10-28T00:00:00Z","timestamp":1130457600000},"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":[[2006,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mantle cell lymphoma (MCL) is characterized by the chromosomal translocation t(11;14)(q13;q32), resulting in overexpression of CCND1 in the vast majority of cases. In addition, alterations of other cell\u2010cycle\u2010regulating signal pathways (CDKN2B\/CDKN2A\u2010CCND1 and ARF\u2010MDM2\u2010TP53) are frequently observed. However, the hierarchy of promoter methylations and genomic alterations as well as the interaction with other cell\u2010cycle regulator CDKN1A is poorly understood. A complete methylation\u2010specific PCR coupled with direct sequencing of 71 MCL patient samples previously characterized for TP53 alterations, Ki67 expression by immunohistochemistry, and other genomic alterations was performed. In contrast to rare <jats:italic>p16<\/jats:italic>(<jats:italic>INK4a<\/jats:italic>) promoter methylation (9%), frequent <jats:italic>p15<\/jats:italic>(<jats:italic>INK4b<\/jats:italic>) (62%) and <jats:italic>p14<\/jats:italic>(<jats:italic>ARF<\/jats:italic>) (70%) promoter methylation was detectable in MCL. In an additional 16% of MCL cases, LOH for <jats:italic>p16<\/jats:italic>(<jats:italic>INK4a<\/jats:italic>) was detected. However, MCL cases with <jats:italic>p15<\/jats:italic>(<jats:italic>INK4b<\/jats:italic>) methylation tended to have lower proliferation (73% vs. 57%), and <jats:italic>p15<\/jats:italic>(<jats:italic>INK4b<\/jats:italic>) and <jats:italic>p14<\/jats:italic>(<jats:italic>ARF<\/jats:italic>) promoter methylation was also detected in normal stem cells. Therefore, epigenetic changes of those genes seem not to represent primary oncogenic mechanisms but physiological mechanisms of cell regulation. The rare <jats:italic>p16<\/jats:italic>(<jats:italic>INK4a<\/jats:italic>) promoter methylation and <jats:italic>p16<\/jats:italic>(<jats:italic>INK4a<\/jats:italic>) genetic alterations were directly correlated to cell proliferation and therefore are regarded as additional molecular alterations involved in the cell\u2010cycle dysregulation of MCL. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/gcc.20277","type":"journal-article","created":{"date-parts":[[2005,10,28]],"date-time":"2005-10-28T20:46:49Z","timestamp":1130532409000},"page":"203-210","source":"Crossref","is-referenced-by-count":34,"title":["Differential effect of epigenetic alterations and genomic deletions of CDK inhibitors [<i>p16<\/i>(<i>INK4a<\/i>), <i>p15<\/i>(<i>INK4b<\/i>), <i>p14<\/i>(<i>ARF<\/i>)] in mantle cell lymphoma"],"prefix":"10.1002","volume":"45","author":[{"given":"Grit","family":"Hutter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Scheubner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Zimmermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joerg","family":"Kalla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiemo","family":"Katzenberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"H\u00fcbler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Roth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Hiddemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"German","family":"Ott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Dreyling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,10,28]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1044-579X(02)00053-6"},{"key":"e_1_2_6_3_1","first-page":"2409","article-title":"BMI\u20101 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