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Title: | Unraveling the genetics of transformed splenic marginal zone lymphoma |
Author: | Grau, Marta López, Cristina Navarro, Alba Frigola, Gerard Nadeu, Ferran Clot, Guillem Bastidas Mora, Gabriela Alcoceba, Miguel Baptista, Maria Joao Blanes, Margarita Colomer, Dolors Costa, Dolors Domingo Domènech, Eva Enjuanes, Anna Escoda, Lourdes Forcada, Pilar Giné Soca, Eva López Guerra, Mónica Ramón, Olga Rivas Delgado, Alfredo Vicente Folch, Laura Wotherspoon, Andrew Climent, Fina Campo, Elías López Guillermo, Armando Matutes, Estella Beà Bobet, Sílvia M. |
Keywords: | Leucèmia limfocítica crònica Genòmica Genomics Chronic lymphocytic leukemia |
Issue Date: | 18-Jul-2023 |
Publisher: | American Society of Hematology |
Abstract: | The genetic mechanisms associated with splenic marginal zone lymphoma (SMZL) transformation are not well defined. We studied 41 patients with SMZL that eventually underwent large B-cell lymphoma transformation. Tumor material was obtained either only at diagnosis (9 patients), at diagnosis and transformation (18 patients), and only at transformation (14 patients). Samples were categorized in 2 groups: (1) at diagnosis (SMZL, n = 27 samples), and (2) at transformation (SMZL-T, n = 32 samples). Using copy number arrays and a next-generation sequencing custom panel, we identified that the main genomic alterations in SMZL-T involved TNFAIP3, KMT2D, TP53, ARID1A, KLF2, 1q gains, and losses of 9p21.3 (CDKN2A/B) and 7q31-q32. Compared with SMZL, SMZL-T had higher genomic complexity, and higher incidence of TNFAIP3 and TP53 alterations, 9p21.3 (CDKN2A/B) losses, and 6p gains. SMZL and SMZL-T clones arose by divergent evolution from a common altered precursor cell that acquired different genetic alterations in virtually all evaluable cases (92%, 12 of 13 cases). Using whole-genome sequencing of diagnostic and transformation samples in 1 patient, we observed that the SMZL-T sample carried more genomic aberrations than the diagnostic sample, identified a translocation t(14;19)(q32;q13) present in both samples, and detected a focal B2M deletion due to chromothripsis acquired at transformation. Survival analysis showed that KLF2 mutations, complex karyotype, and International Prognostic Index score at transformation were predictive of a shorter survival from transformation (P = .001; P = .042; and P = .007; respectively). In summary, SMZL-T are characterized by higher genomic complexity than SMZL, and characteristic genomic alterations that could represent key players in the transformation event. |
Note: | Reproducció del document publicat a: https://doi.org/10.1182/bloodadvances.2022009415 |
It is part of: | Blood Advances, 2023, vol. 7, num. 14, p. 3695-3709 |
URI: | http://hdl.handle.net/2445/202013 |
Related resource: | https://doi.org/10.1182/bloodadvances.2022009415 |
ISSN: | 2473-9537 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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