Cytogenetic aberrations and their prognostic value in a series of 330 splenic marginal zone B-cell lymphomas: a multicenter study of the Splenic B-Cell Lymphoma Group

Abstract

We conducted a retrospective collaborative study to cytogenetically characterize splenic marginal zone lymphoma (SMZL) and ascertain the prognostic value of chromosomal aberrations. Of 330 cases, 72% displayed an aberrant karyotype, 53% were complex, and 29% had a single aberration. The predominant aberrations were gains of 3/3q and 12q, deletions of 7q and 6q and translocations involving 8q/1q/14q. CD5 expression was detected in 39 of 158 cases (25%). The cytogenetic makeup of the CD5 ؉ group differed significantly from that of the CD5 ؊ group. Cases with unmutated IGHV were significantly associated with deletions of 7q and TP53. A strong association was noted between usage of the IGVH1-2 and deletion 7q, 14q alterations, and abnormal karyotype. On univariate analysis, patients with more than or equal to 2 aberrations, 14q alterations, and TP53 deletions had the shortest survival; 7q deletion did not affect survival. On multivariate analysis, cytogenetic aberrations did not retain prognostic significance; the parameters negatively affecting survival were hemoglobin and age. In conclusion, the cytogenetic profile of SMZL is distinct from other B-cell lymphomas. Complexity of the karyotype, 14q aberrations, and TP53 deletions are poor prognostic indicators and may be considered together with other clinicobiologic parameters to ascertain the prognosis of SMZL. (Blood. 2010;

Splenic marginal zone lymphoma: comprehensive analysis of gene expression and miRNA profiling

“…The finding is consistent with the recently published results showing 14q alterations in splenic marginal zone lymphoma, 6 which are also associated with poor prognosis. 46 Downregulation of these miRNAs could also be involved in the growth and progression of splenic marginal zone lymphoma through the regulation of oncogenic target genes such as MUM1, FOXP1, SYK and BCL2.…”

Over 30% of patients with splenic marginal zone lymphoma express the same immunoglobulin heavy variable gene: ontogenetic implications

“…1 Some cytogenetic, molecular and clinical information has been reported previously. 10,13,16,22 The study was conducted in accordance with the Declaration of Helsinki and approved by the local Ethics Committee of each institution.…”

“…21 Furthermore, some studies have also examined whether particular molecular characteristics of the IG receptors might be associated with genetic or phenotypic features, and/or clinical outcome. However, owing to their retrospective nature, definitive conclusions cannot be drawn, except possibly for certain genomic aberrations, which have been detected with higher frequency among IGHV-unmutated cases (especially, deletion of chromosome 7q 10,20,22 and/or cases expressing particular IGHV genes). 20,22 With few exceptions, 21,22 most relevant publications have been based on the analysis of relatively small series.…”

“…However, owing to their retrospective nature, definitive conclusions cannot be drawn, except possibly for certain genomic aberrations, which have been detected with higher frequency among IGHV-unmutated cases (especially, deletion of chromosome 7q 10,20,22 and/or cases expressing particular IGHV genes). 20,22 With few exceptions, 21,22 most relevant publications have been based on the analysis of relatively small series. Furthermore, the inclusion criteria and types of tissue specimens examined varied significantly, introducing classification uncertainties (for example, when spleen histology was unavailable) and/or selection biases (for example, by analyzing exclusively blood or spleen specimens).…”

Whole genome profiling and other high throughput technologies in lymphoid neoplasms—current contributions and future hopes

“…Interstitial losses of 7q are a frequent finding in splenic MZL (SMZL) but less frequent in MCL and rare in CLL or other small B-cell lymphomas. 12,20 Differences in genomic profiles have also been observed in different types of peripheral T (PTCL) and NK-cell lymphomas. PTCL -NOS and angioimmunoblastic T-cell lymphoma (AITL) share gains in chromosome 8, 9, and 19 and losses in chromosome 2 but also vary in different regions.…”