GENES, CHROMOSOMES & CANCER 00:000–000 (2010) Incidence and Prognostic Impact of Secondary Cytogenetic Aberrations in a Series of 145 Patients with Mantle Cell Lymphoma Blanca Espinet, 1 * † Itziar Salaverria, 2,3† S  ılvia Bea `, 2 Neus Ruiz-Xiville ´, 4 Olga Balague ´, 2 Marta Salido, 1 Dolors Costa, 2 Joaquim Carreras, 2 Ana Eugenia Rodr  ıguez-Vicente, 5 Juan Lu  ıs Garc  ıa, 5 Jesu ´s Mar  ıa Herna ´ ndez-Rivas, 5 Mar  ıa Jose ´ Calasanz, 6 Reiner Siebert, 3 Ana Ferrer, 1 Antonio Salar, 1 Ana Carrio ´, 2 Natividad Polo, 7 Jose ´ Antonio Garc  ıa-Marco, 7 Alicia Domingo, 8 Eva Gonza ´lez-Barca, 8 Vicenc ¸ Romagosa, 8 Isabel Maruga ´n, 9 Armando Lo ´ pez-Guillermo, 2 Fuensanta Milla ´, 4 Jose ´ Lu  |s Mate, 4 Elisa Lun ˜ o, 10 Carmen Sanzo, 10 Rosa Collado, 11 Isabel Oliver, 11 Sebastia ` Monzo ´, 12 Antonio Palac  |n, 2 Teresa Gonza ´lez, 13 Francesc Sant, 14 Ramon Salinas, 14 Mar  ıa Teresa Ardanaz, 15 Llorenc ¸ Font, 16 Lourdes Escoda, 17 Lourdes Florensa, 1 Sergi Serrano, 1 Elias Campo, 2 and Francesc Sole ´ 1 1 Laboratori de Citogene' tica Molecular, Laboratori de Citologia Hematolo' gica, Servei de Patologia, Servei d’Hematologia Cl  |nica, GRETNHE, IMIM-Hospital del Mar,Barcelona, Spain 2 Seccio¤ d’Hematopatologia,Hospital Cl  |nic, Institut d’Investigacions Biome' diques August Pi i Sunyer (IDIBAPS),Universitat de Barcelona,Barcelona, Spain 3 Institute of Human Genetics,University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University,Kiel,Germany 4 Servei Laboratori d’Hematologia, Servei d’Anatomia Patolo' gica,Institut Catala' d’Oncologia-Hospital Universitari GermansTrias i Pujol,Badalona, Spain 5 Servicio de Hematologia, Hospital Universitario de Salamanca, IBMCC,Centro de Investigacio¤ n del Ca¤ ncer,Universidad de Salamanca,CSIC, Salamanca, Spain 6 Servicio de Citogene¤ tica, Departamento de Gene¤ tica,Universidad de Navarra, Pamplona, Spain 7 Unidad de Citogenetica Molecular, Servicio de Hematologia, Hospital Universitario Puerta de Hierro, Madrid, Spain 8 Servei d’Hematologia, Servei d’Hematologia Cl  |nica, Servei de Patologia, IDIBELL-Hospital de Bellvitge, L’Hospitalet de Llobregat, Spain 9 Servicio de Hematolog  |a y Oncolog  |a Me¤ dica, Hospital Cl  |nico Universitario,Valencia, Spain 10 Servicio de Hematolog  |a, Hospital Universitario Central de Asturias,Oviedo, Spain 11 Servicio de Hematolog  |a,Consorcio Hospital General Universitario,Valencia, Spain 12 Servei d’Hematologia, Hospital Universitari Sagrat Cor,Barcelona, Spain 13 Fundacio¤ n Pu¤ blica Galega de Medicina Xeno¤ mica, Santiago de Compostela, Spain 14 Servei d’Anatomia Patolo' gica, Servei d’Hematologia Cl  |nica, Althaia-Xarxa Assistencial de Manresa, Manresa, Spain 15 Servicio de Hematolog  |a, Hospital Txagorritxu,Vitoria, Spain 16 Servei d’Hematologia, Hospital Verge de la Cinta,Tortosa, Spain 17 Servei d’Hematologia, Hospital Joan XXIII,Tarragona, Spain Mantle cell lymphoma (MCL) is a mature B-cell neoplasm with an aggressive behavior, characterized by the t(11;14)(q13;q32). Several secondary genetic abnormalities with a potential role in the oncogenic process have been described. Studies of large MCL series using conventional cytogenetics, and correlating with proliferation and survival, are scarce. We selected 145 MCL cases at diagnosis, displaying an aberrant karyotype, from centers belonging to the Spanish Cooperative Group for Hematological Cytogenetics. Histological subtype, proliferative index and survival data were ascer- tained. Combined cytogenetic and molecular analyses detected CCND1 translocations in all cases, mostly t(11;14)(q13;q32). Secondary aberrations were present in 58% of patients, the most frequent being deletions of 1p, 13q and 17p, 10p altera- tions and 3q gains. The most recurrent breakpoints were identified at 1p31-32, 1p21-22, 17p13, and 1p36. Aggressive blas- toid/pleomorphic variants displayed a higher karyotypic complexity, a higher frequency of 1p and 17p deletions and 10p alterations, a higher proliferation index and poor survival. Gains of 3q and 13q and 17p13 losses were associated with reduced survival times. Interestingly, gains of 3q and 17p losses added prognostic significance to the morphology in a multi- variate analysis. Our findings confirm previous observations indicating that proliferation index, morphology and several sec- y The first two authors contributed equally to the study. Supported by: subprograma RETICS, Fondo de Investigacio ´n Sanitaria, Instituto de Salud Carlos III; Spanish Ministry of Health, Grant numbers: RD07/0020/2004; 2006RET2039; Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Science, Innovation; the Cancer Research Foundation of Salamanca University (Accio ´ n Transversal del Ca ´ ncer), Spain; Alexander Von Humboldt Foundation. *Correspondence to: Blanca Espinet, PhD, Laboratori de Cito- gene `tica Molecular, Servei de Patologia, Hospital del Mar, Barce- lona 08003, Spain. E-mail: bespinet@imas.imim.es Received 10 September 2009; Accepted 4 January 2010 DOI 10.1002/gcc.20754 Published online in Wiley InterScience (www.interscience.wiley.com). RESEARCH ARTICLE V V C 2010 Wiley-Liss, Inc.