{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:24:28Z","timestamp":1790619868762,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2018,9,11]],"date-time":"2018-09-11T00:00:00Z","timestamp":1536624000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Trisomy 12 (tri12) is the second most frequent chromosomal aberration (15%\u201020%) in chronic lymphocytic leukemia (CLL). Tri12 confers an intermediate prognosis but is a heterogeneous entity. We examined whether additional mutational or chromosomal alterations might impact tri12 patient outcomes. This retrospective study, carried out by the French Innovative Leukemia Organization, included 188 tri12 patients with comprehensive information on immunoglobulin heavy chain (<jats:italic>IGHV<\/jats:italic>) gene status, karyotypic\/FISH abnormalities, and <jats:italic>NOTCH1<\/jats:italic>, <jats:italic>TP53<\/jats:italic>, <jats:italic>SF3B1<\/jats:italic>, and <jats:italic>MYD88<\/jats:italic> mutations. The main cytogenetic abnormalities associated with tri12 were del(13q) (25%), additional trisomies (14%) (including tri19 (10%) and tri18 (4%)), 14q32 translocations (10%), del(17p) (6.5%), del(14q) (4%), and del(11q) (4%). Unmutated (UM) <jats:italic>IGHV<\/jats:italic>, <jats:italic>NOTCH1<\/jats:italic>, and <jats:italic>TP53<\/jats:italic>, mutations were identified in respectively 66%, 25%, and 8.5% of cases. Multivariate analyses showed that additional trisomies (HR\u2009=\u20090.43, 95% CI\u2009=\u20090.23\u20100.78, <jats:italic>P<\/jats:italic>\u2009=\u2009.01) were associated with a significantly longer time to first treatment in Binet stage A patients and with a lower risk of relapse (HR\u2009=\u20090.37, 95% CI\u2009=\u20090.15\u20100.9, <jats:italic>P<\/jats:italic>\u2009=\u2009.03) in the overall tri12 population. Binet stage B\/C, <jats:italic>TP53<\/jats:italic> disruption, and UM <jats:italic>IGHV<\/jats:italic> status were associated with a shorter time to next treatment, while Binet stage B\/C (HR\u2009=\u20094, 95% CI\u2009=\u20091.6\u20104.9, <jats:italic>P<\/jats:italic>\u2009=\u2009.002) and <jats:italic>TP53<\/jats:italic> disruption (HR\u2009=\u20095, 95% CI\u2009=\u20091.94\u201012.66, <jats:italic>P<\/jats:italic>\u2009=\u2009.001) conferred shorter overall survival in multivariate comparisons. These data indicate that additional cytogenetic and mutational abnormalities, and particularly additional trisomies, <jats:italic>IGHV<\/jats:italic> status, and <jats:italic>TP53<\/jats:italic> disruption, influence tri12 patient outcomes and could improve risk stratification in this population.<\/jats:p>","DOI":"10.1002\/gcc.22650","type":"journal-article","created":{"date-parts":[[2018,9,11]],"date-time":"2018-09-11T16:08:07Z","timestamp":1536682087000},"page":"533-540","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Mutational and cytogenetic analyses of 188 CLL patients with trisomy 12: A retrospective study from the French Innovative Leukemia Organization (FILO) working group"],"prefix":"10.1002","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7767-755X","authenticated-orcid":false,"given":"Damien","family":"Roos\u2010Weil","sequence":"first","affiliation":[{"name":"Sorbonne Universit\u00e9s, UPMC Univ Paris 06, AP\u2010HP, GRC\u201011, Groupe de recherche clinique sur les h\u00e9mopathies lympho\u00efdes (GRECHY), H\u00f4pital Piti\u00e9\u2010Salp\u00e9tri\u00e8re, APHP  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Nguyen\u2010Khac","sequence":"additional","affiliation":[{"name":"Service d'H\u00e9matologie Biologique H\u00f4pital Piti\u00e9\u2010Salp\u00eatri\u00e8re, APHP  Paris France"},{"name":"Centre de Recherche des Cordeliers INSERM UMRS 1138, Cell Death and Drug Resistance in Lymphoproliferative Disorders Team  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Chevret","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Biostatistique et Informatique M\u00e9dicale (DBIM) H\u00f4pital Saint Louis, APHP  Paris 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