{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:19:01Z","timestamp":1790831941046,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2006,10,11]],"date-time":"2006-10-11T00:00:00Z","timestamp":1160524800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2006,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>DNA licensing is a crucial process for chromosome replication control. Deregulation of the licensing factors <jats:italic>Cdt1<\/jats:italic>, <jats:italic>Cdc6<\/jats:italic> and the licensing inhibitor <jats:italic>geminin<\/jats:italic> has been associated with DNA replication defects and chromosomal instability. We examined the expression of these factors, in mantle cell lymphoma (MCL) and non\u2010neoplastic lymphoid samples, and analysed the potential role of their deregulation in genomic instability. <jats:italic>Geminin<\/jats:italic>, <jats:italic>Cdt1<\/jats:italic> and <jats:italic>Cdc6<\/jats:italic> were coordinately expressed in non\u2010neoplastic tissues and most MCL in relationship to the proliferative activity of the cells. However, 6 (18%) tumours showed an unbalanced \u201clicensing signature\u201d characterized by a higher expression of <jats:italic>Cdt1<\/jats:italic> and <jats:italic>Cdc6<\/jats:italic> than the negative regulator <jats:italic>geminin<\/jats:italic>. Tumours with this unbalanced signature and <jats:italic>p53\/p14<jats:sup>ARF<\/jats:sup><\/jats:italic> alterations had significantly higher number of chromosome abnormalities than lymphomas with <jats:italic>p53\/p14<jats:sup>ARF<\/jats:sup><\/jats:italic> alterations but with a normal licensing signature. No aberrations of <jats:italic>Cdct1<\/jats:italic>, <jats:italic>Cdc6<\/jats:italic>, and <jats:italic>geminin<\/jats:italic> genes were detected in cases with unbalanced licensing. However, tumours with p53\/ARF inactivation and unbalanced licensing signature had significantly higher cyclin D1 levels than tumours with normal licensing signature. These results suggest that an unbalanced mRNA expression of licensing regulatory genes may play a role in the pathogenesis of the chromosomal instability of a subset of MCL with inactivation of the <jats:italic>p53\/p14<jats:sup>ARF<\/jats:sup><\/jats:italic> pathway. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.22146","type":"journal-article","created":{"date-parts":[[2006,10,11]],"date-time":"2006-10-11T20:36:40Z","timestamp":1160599000000},"page":"2768-2774","source":"Crossref","is-referenced-by-count":31,"title":["Unbalanced expression of licensing DNA replication factors occurs in a subset of mantle cell lymphomas with genomic 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