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Página principal > Artículos > Artículos publicados > Unraveling the genetics of transformed splenic marginal zone lymphoma |
Fecha: | 2023 |
Resumen: | 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. |
Ayudas: | Instituto de Salud Carlos III PI17/ 01061 Instituto de Salud Carlos III PI19/00887 Agència de Gestió d'Ajuts Universitaris i de Recerca 2021-SGR-01293 Agència de Gestió d'Ajuts Universitaris i de Recerca 2021-SGR-01172 Agencia Estatal de Investigación PID2021-123054OB-I00 |
Nota: | Altres ajuts: Fundació La Marató de TV3 (201904-30) |
Derechos: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades. |
Lengua: | Anglès |
Documento: | Article ; recerca ; Versió publicada |
Publicado en: | Blood advances, Vol. 7 Núm. 14 (july 2023) , p. 3695-3709, ISSN 2473-9537 |
15 p, 3.6 MB |