biostudies-literatureNadeu FEuropean Hematology AssociationNCI NIH HHS1419-1432https://www.ebi.ac.uk/biostudies/studies/S-EPMC7498364biostudies-literatureUnknown136(12)Mantle cell lymphoma (MCL) is a mature B-cell neoplasm initially driven by CCND1 rearrangement with 2 molecular subtypes, conventional MCL (cMCL) and leukemic non-nodal MCL (nnMCL), that differ in their clinicobiological behavior. To identify the genetic and epigenetic alterations determining this diversity, we used whole-genome (n = 61) and exome (n = 21) sequencing (74% cMCL, 26% nnMCL) combined with transcriptome and DNA methylation profiles in the context of 5 MCL reference epigenomes. We identified that open and active chromatin at the major translocation cluster locus might facilitate the t(11;14)(q13;32), which modifies the 3-dimensional structure of the involved regions. This translocation is mainly acquired in precursor B cells mediated by recombination-activating genes in both MCBloodGenomic and epigenomic insights into the origin, pathogenesis, and clinical behavior of mantle cell lymphoma subtypes.PMC7498364RG5P01 CA229100Bea SKulis MSiebert RChapaprieta VTorrents DDiaz-Navarro AColomer DPuiggros MAymerich MCosta DCastellano GJares PValdes-Mas RDuran-Ferrer MMartin-Subero JIVilarrasa-Blasi RLopez CNadeu FPuente XSKuppers RNavarro AMuntanola AEspinet BRoyo RGutierrez-Abril JClot GCampo ERibera-Cortada IMartin-Garcia DLopez-Guillermo AGine EfalseGenomic and epigenomic insights into the origin, pathogenesis, and clinical behavior of mantle cell lymphoma subtypes.Mantle cell lymphoma (MCL) is a mature B-cell neoplasm initially driven by CCND1 rearrangement with 2 molecular subtypes, conventional MCL (cMCL) and leukemic non-nodal MCL (nnMCL), that differ in their clinicobiological behavior. To identify the genetic and epigenetic alterations determining this diversity, we used whole-genome (n = 61) and exome (n = 21) sequencing (74% cMCL, 26% nnMCL) combined with transcriptome and DNA methylation profiles in the context of 5 MCL reference epigenomes. We identified that open and active chromatin at the major translocation cluster locus might facilitate the t(11;14)(q13;32), which modifies the 3-dimensional structure of the involved regions. This translocation is mainly acquired in precursor B cells mediated by recombination-activating genes in both MC2020-01-01T00:00:00Z2020 Sep2026-05-02T15:02:28.198Z2020-09-30T07:03:48ZS-EPMC74983643258497010.1182/blood.2020005289