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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, Eva
Lopez-guerra, Mónica
Ramón, Olga
Rivas-delgado, Alfredo
Vicente Folch, Laura
Wotherspoon, Andrew
Climent, Fina
Campo, Elias
López-guillermo, Armando
Matutes, Estella
Beà, Sílvia
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.
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It is part of: Blood Advances, 2023, vol. 7, issue. 14, p. 3695-3709
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Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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