Secondary chromosome changes in mantle cell lymphoma: cytogenetic and fluorescence in situ hybridization studies

To better define the incidence and nature of secondary chromosome anomalies in mantle cell lymphoma (MCL) carrying the t(11:14)/BCL1 rearrangement, cytogenetic and fluorescence in situ hybridization studies (FISH) were performed in 42 patients (39 classical histology, 3 blastoid variant), using 6q21, 9p21/p16, 13q14, 17p13/p53 and chromosome-12-specific probes. Karyotypes from 89 cases published in 5 recent series including patients diagnosed in a homogeneous fashion were reviewed. In our series, FISH confirmed the interpretation of the karyotype in all cases and disclosed cryptic chromosome deletions in a sizeable fraction of cases. One patient (2.4% of total) was found with a cryptic 9p21 deletion by FISH. Two cases (4.8%) had a 6q21 deletion at CCA and at FISH; +12 was found in three cases by CCA plus nine by FISH (28.6%); 13q14 deletion was found in six cases by CCA plus 16 by FISH (52.4%), 17p13 deletion in three cases by CCA plus 8 by FISH (26.2%). In 131 patients (42 present series plus 89 in the literature) secondary chromosome aberrations seen by conventional cytogenetic analysis in more than 5 cases included deletions/translocations (del/t) 6q15-23 [15 cases]; -13 [14 cases]; del/t 1p21-31 [12 cases]; +3q [11 cases]; del/t 17p [9 cases]; 8p translocations and del(Y) [8 cases each]; -20 [7 cases]; 13q14 deletion, del/t 11q22-23, del/t 9q, del(10)(q22q24), -20, -21, -22 and -X [6 cases each]. We arrived at the following conclusions: i) though no secondary anomaly is specific for MCL, there is a distinct profile of recurrent chromosome lesions in MCL with 1p21-31 deletions, 8p translocations, 11q22-23 anomalies having a strong association with CD5+ B-cell lymphomas of low-to-intermediate grade histology; ii) FISH enabled the detection of cryptic chromosome 12, 13q and 17p rearrangements in a sizeable fraction of cases; iii) 9p21/p16 deletions did not occur at a high incidence in this series, possibly because of the low number of cases with blastoid variant.