دورية أكاديمية
Unraveling the genetics of transformed splenic marginal zone lymphoma
| العنوان: | Unraveling the genetics of transformed splenic marginal zone lymphoma |
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| المؤلفون: | 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, Mònica, Ramón, Olga, Rivas Delgado, Alfredo, Vicente Folch, Laura, Wotherspoon, Andrew, Climent, Fina, Campo, Elías, López Guillermo, Armando, Matutes, Estella, Beà Bobet, Sílvia M. |
| المصدر: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
| بيانات النشر: | American Society of Hematology |
| سنة النشر: | 2023 |
| المجموعة: | Dipòsit Digital de la Universitat de Barcelona |
| مصطلحات موضوعية: | Leucèmia limfocítica crònica, Genòmica, Genomics, Chronic lymphocytic leukemia |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | 15 p.; application/pdf |
| اللغة: | English |
| تدمد: | 2473-9537 |
| العلاقة: | Reproducció del document publicat a: https://doi.org/10.1182/bloodadvances.2022009415Test; Blood Advances, 2023, vol. 7, num. 14, p. 3695-3709; https://doi.org/10.1182/bloodadvances.2022009415Test; http://hdl.handle.net/2445/202013Test |
| الإتاحة: | https://doi.org/10.1182/bloodadvances.2022009415Test http://hdl.handle.net/2445/202013Test |
| حقوق: | cc by-nc-nd (c) Grau, Marta et al., 2023 ; http://creativecommons.org/licenses/by-nc-nd/3.0/esTest/ ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.52DC0E19 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 24739537 |
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