E-resources
-
Nadeu, Ferran; Martin-Garcia, David; Clot, Guillem; Díaz-Navarro, Ander; Duran-Ferrer, Martí; Navarro, Alba; Vilarrasa-Blasi, Roser; Kulis, Marta; Royo, Romina; Gutiérrez-Abril, Jesús; Valdés-Mas, Rafael; López, Cristina; Chapaprieta, Vicente; Puiggros, Montserrat; Castellano, Giancarlo; Costa, Dolors; Aymerich, Marta; Jares, Pedro; Espinet, Blanca; Muntañola, Ana; Ribera-Cortada, Inmaculada; Siebert, Reiner; Colomer, Dolors; Torrents, David; Gine, Eva; López-Guillermo, Armando; Küppers, Ralf; Martin-Subero, Jose I.; Puente, Xose S.; Beà, Sílvia; Campo, Elias
Blood, 09/2020, Volume: 136, Issue: 12Journal Article
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 MCL subtypes, whereas in 8% of cases the translocation occurs in mature B cells mediated by activation-induced cytidine deaminase. We identified novel recurrent MCL drivers, including CDKN1B, SAMHD1, BCOR, SYNE1, HNRNPH1, SMARCB1, and DAZAP1. Complex structural alterations emerge as a relevant early oncogenic mechanism in MCL, targeting key driver genes. Breakage-fusion-bridge cycles and translocations activated oncogenes (BMI1, MIR17HG, TERT, MYC, and MYCN), generating gene amplifications and remodeling regulatory regions. cMCL carried significant higher numbers of structural variants, copy number alterations, and driver changes than nnMCL, with exclusive alterations of ATM in cMCL, whereas TP53 and TERT alterations were slightly enriched in nnMCL. Several drivers had prognostic impact, but only TP53 and MYC aberrations added value independently of genomic complexity. An increasing genomic complexity, together with the presence of breakage-fusion-bridge cycles and high DNA methylation changes related to the proliferative cell history, defines patients with different clinical evolution. •The primary CCND1 rearrangement is mediated by the same mechanisms in cMCL and nnMCL, but they differ in the (epi)genetic and driver makeup.•Genomic complexity and DNA methylation changes related to proliferative cell history stratify patients with distinct clinical outcomes. Display omitted
Author
Shelf entry
Permalink
- URL:
Impact factor
Access to the JCR database is permitted only to users from Slovenia. Your current IP address is not on the list of IP addresses with access permission, and authentication with the relevant AAI accout is required.
Year | Impact factor | Edition | Category | Classification | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Select the library membership card:
If the library membership card is not in the list,
add a new one.
DRS, in which the journal is indexed
Database name | Field | Year |
---|
Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
---|
Source: Personal bibliographies
and: SICRIS
The material is available in full text. If you wish to order the material anyway, click the Continue button.