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blooda_adv-2022-009415-main.pdf (3.62 MB)

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2023-07-18

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cc by-nc-nd (c) Grau, Marta et al., 2023
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/202013

Unraveling the genetics of transformed splenic marginal zone lymphoma

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https://doi.org/10.1182/bloodadvances.2022009415

Resum

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.

Matèries

Leucèmia limfocítica crònica, Genòmica, Genomics

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Chronic lymphocytic leukemia

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Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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GRAU, Marta, LÓPEZ GONZÁLEZ, Cristina, NAVARRO, Alba, FRIGOLA, Gerard, NADEU PRAT, Ferran, CLOT RAZQUIN, Guillem, BASTIDAS MORA, Gabriela, ALCOCEBA, Miguel, BAPTISTA, Maria joao, BLANES, Margarita, COLOMER PUJOL, 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 GÜERRI, Elias, LÓPEZ GUILLERMO, Armando, MATUTES, Estella, BEÀ BOBET, Sílvia m.. Unraveling the genetics of transformed splenic marginal zone lymphoma. _Blood Advances_. 2023. Vol. 7, núm. 14, pàgs. 3695-3709. [consulta: 24 de gener de 2026]. ISSN: 2473-9537. [Disponible a: https://hdl.handle.net/2445/202013]

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