Background: Mantle cell lymphoma (MCL) is a heterogeneous disease still lacking reliable prognostic factors. A recurrent feature of this disease is however the t(11;14) translocation, yielding an increased production of Cyclin D1 through activation by the IGH promoter. In a previous study based on a controlled randomized trial (LyMA study, #113303; presented at ASH 2017 and currently submitted) we observed that large gains on chromosome 11, identified by single nucleotide polymorphisms (SNP), in a region always including the CCND1 locus encoding for cyclin D1, were related to a worse prognosis. In this series of 94 lymph node biopsies, this anomaly was observed in 7 patients who displayed a significantly worse outcome (p=0.004) Aims: Here we examined a real-life cohort of MCL patients who benefited from fluorescence in situ hybridization (FISH), to assess whether chromosome 11 gains indeed impacted outcome.Methods: All patients intensively treated between 1995 and 2018 with an assessment of CCND1 gains by FISH analysis were included.Fifty-one patients were consolidated with an autograft similar to that applied in the LyMA trial. Patients with FISH results suggestive of tetraploidy were considered separately. Outcomes were established as the delay between the initiation of the first line treatment and first relapse, death or last news. Results: A cohort of 65 MCL patients was included with a median age of 58 years old (range 34-74) and a M/F ratio of 2,1. Seventeen patients displayed a significant signal suggesting CCND1 or fusion gain. FISH signals were interpreted as normal wild type chromosome, fusion signals and extraneous (supernumerary) signals. When considering patients with extra CCND1 or fusion signals, compared with patients with an expected classical translocation signal, a significantly worse outcome was observed in terms of progression free survival (PFS) with respective medians of 30 vs 116 months (HR=2.4[1.0-5.7];p=0.05). Moreover, when removing patients likely to present tetraploidy (i.e. double translocation load associated with whole genome increase), the significance of these gains reached a significance of p=0.02 (25 vs 116 months; HR=3.2[1.2-8.7]). Conclusions: Although the t(11;14) translocation is an undisputed hallmark of MCL diagnosis, in an integrated approach of morphological and immunophenotypic features, closer examination of FISH signals could provide an additional prognosis factor, as suggested by SNP analysis but not systematically requiring it. Introduction and aim of study: Mantle cell lymphoma (MCL) is a distinct subtype of non-Hodgkin lymphoma, and the mechanism of its development is still not fully elucidated. Most of mantle cell lymphoma did not undergo germinal center reaction such as somatic hypermutation. Interestingly, prior immunoglobulin sequencing has noted that there are several stereotypes of V(D)J recombination, hypothesizing that these stereotypes might result from unknown biased selection. This study took advantage of next generation sequencing (NGS) to characteriz...

We report the first case of a nodal marginal zone large B-cell lymphoma and the first with MYC rearrangement. This high proliferation rate lymphoma (40% of cells) occurred in the bilateral cervical, axillary, and para-aortic lymph nodes of an 82 year old woman. It involved extensively her bone marrow, and was lethal. Malignant B-cells were CD10 negative, harbored Burkitt translocation, and multiple chromosomal changes including trisomies of chromosomes 3 and 18, and three copies of 8q with an intact q24 cytoband (in addition to MYC rearrangement), associated with overexpression of BCL6, BCL2, and MYC respectively. We suggest that in aggressive nodular marginal zone lymphomas (clinical picture or high proliferation rate of lymphoma cells), fluorescence in situ hybridization analysis for MYC rearrangement, with break-apart probe, and for MYC/IGH translocation, in addition to chromosome analysis, should be performed. MYC rearrangement associated with a more rapid progression of the neoplasia, might warrant a more aggressive treatment. 〔J Clin Exp Hematop 55(3) : 175-180, 2015〕