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862610.pdf (3.62 MB)

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2024-07-11
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/221948

SOX11 expression is restricted to EBV-negative Burkitt lymphoma and associates with molecular genetic features

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SRY-related HMG-box gene 11 (SOX11) is a transcription factor overexpressed in mantle cell lymphoma (MCL), a subset of Burkitt lymphomas (BL) and precursor lymphoid cell neoplasms but is absent in normal B cells and other B-cell lymphomas. SOX11 has an oncogenic role in MCL but its contribution to BL pathogenesis remains uncertain. Here, we observed that the presence of Epstein-Barr virus (EBV) and SOX11 expression were mutually exclusive in BL. SOX11 expression in EBV-negative (EVB-) BL was associated with an IG∷MYC translocation generated by aberrant class switch recombination, whereas in EBV-negative (EBV-)/SOX11-negative (SOX11-) tumors the IG∷MYC translocation was mediated by mistaken somatic hypermutations. Interestingly, EBV- SOX11-expressing BL showed higher frequency of SMARCA4 and ID3 mutations than EBV-/SOX11- cases. By RNA sequencing, we identified a SOX11-associated gene expression profile, with functional annotations showing partial overlap with the SOX11 transcriptional program of MCL. Contrary to MCL, no differences on cell migration or B-cell receptor signaling were found between SOX11- and SOX11-positive (SOX11+) BL cells. However, SOX11+ BL showed higher adhesion to vascular cell adhesion molecule 1 (VCAM-1) than SOX11- BL cell lines. Here, we demonstrate that EBV- BL comprises 2 subsets of cases based on SOX11 expression. The mutual exclusion of SOX11 and EBV, and the association of SOX11 with a specific genetic landscape suggest a role of SOX11 in the early pathogenesis of BL.

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Matèries

Virus, Duplicació de l'ADN, Limfomes, Factors de transcripció, Genètica

Matèries (anglès)

Viruses, DNA replication, Lymphomas, Transcription factors, Genetics

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Articles publicats en revistes (Fonaments Clínics)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Citació

SUREDA GÓMEZ, Marta, IACCARINO, Ingram, BOLÒS, Anna de, MEYER, Mieke, BALSAS, Patricia, RICHTER, Julia, RODRÍGUEZ, Marta-leonor, LÓPEZ GONZÁLEZ, Cristina, CARRERAS-CABALLÉ, Maria, GLASER, Selina, NADEU PRAT, Ferran, JARES GERBOLES, Pedro, CLOT RAZQUIN, Guillem, SICILIANO, Maria chiara, BELLAN, Cristina, TORNAMBÈ, Salvatore, BOCCACCI, Roberto, LEONCINI, Lorenzo, CAMPO GÜERRI, Elias, SIEBERT, Reiner, AMADOR ESPINOSA, Virginia, KLAPPER, Wolfram. SOX11 expression is restricted to EBV-negative Burkitt lymphoma and associates with molecular genetic features. _Blood_. 2024. Vol. 144, núm. 2, pàgs. 187-200. [consulta: 26 de novembre de 2025]. ISSN: 0006-4971. [Disponible a: https://hdl.handle.net/2445/221948]

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