Analysis of Cytogenetic Abnormalities and Their Prognostic Impact in a Series of 145 Mantle Cell Lymphoma Cases with An Abnormal Karyotype.
Authors: Espinet Blanca , Itziar Salaverría , Beà Sílvia , Ruiz-Xivillé Neus , Balagué Olga , Salido Marta , Costa Dolors , Rodriguez Ana E , García Juan LuíS. , Hernández-Rivas JesúS. M.ª , Calasanz M.ª José , Ferrer Ana M , Salar Antonio , Carrió Ana , Polo Natividad , García-Marco Jose Antonio , Domingo Alicia , González-Barca Eva , Romagosa Vicenç , Marugán Isabel , López-Guillermo Armando , Millá Fuensanta , Mate José Luís , Luño Elisa , Sanzo Carmen , Collado Rosa , Oliver Isabel , Monzó Sebastià , Palacín Antonio , González Teresa , Sant Francesc , Salinas Ramon , Ardanaz Mª Teresa , Font Llorenç , Escoda Lourdes , Florensa Lourdes , Campo Elias , Serrano Sergi , Solé Francesc 
Published: April 2020

Abstract
INTRODUCTION. Mantle cell lymphoma (MCL) is a well defined mature B-cell neoplasm, usually with an aggressive behaviour and a median survival of 3–5 years. It is characterized by the presence of t(11;14)(q13;q32), that leads to overexpression of CCND1. This translocation is detected by conventional cytogenetics (CC) in more than 65% of the cases. Nevertheless, cyclin D1 overexpression alone is not sufficient to give rise to a MCL. Several secondary genetic abnormalities with a potential role in the oncogenic process have been described using different molecular and cytogenetic techniques but no data from large series of MCL cases studied by CC have been correlated with survival and proliferation information.
AIMS. 1. To correlate secondary chromosomal abnormalities, histological subtype and proliferative index with survival. 2. To describe the frequency of secondary chromosomal aberrations using CC and a large series of MCL patients.
PATIENTS AND METHODS. We selected 145 MCL cases (94M/51F; mean age 65.4 yrs; mean survival 33 mo.), all of them with an abnormal karyotype. Histological subtype, proliferative index (Ki-67) and survival data were collected. All patients were studied by conventional GTG-banding cytogenetics, and FISH with a dual colour dual fusion CCND1/IGH probe was applied in those cases with an abnormal karyotype but without t(11;14) detected by CC.
RESULTS. Translocation t(11;14) was detected as a single anomaly in 36% of patients, whereas 57% of cases displayed t(11;14) plus other additional aberrations and 6% of patients showed an abnormal karyotype without t(11;14) which was detected by FISH. We observed a total of 550 abnormalities (147 numerical and 403 structural), being the most frequent deletions of 1p (12%), 13q and 17p (10% each) and gains of 3q (9%). Recurrent breakpoints were identified at 1p31–p32, 1p21–p22, 17p13 and 1p36 (in eight, six, five and four cases, respectively). Blastoid variants of MCL displayed more karyotypic complexity with high number of structural alterations, higher number of 1p and 17p deletions, higher proliferation index and poor survival.
CONCLUSIONS. 1. MCL cases associated with 17p losses (overall survival at 4 yrs: 15% vs 50%; P=0.01) and high proliferative index (15% vs 55%; P=0.005), generally corresponding to blastoid variants, display a worse outcome. 2. Our results confirm, by means of a routine technique as CC, previous observations made using more sophisticated molecular techniques in shorter series of patients.