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

Abstract

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- BL was associated with an IG∷MYC translocation generated by aberrant class switch recombination, while in EBV-/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 compared to 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 BCR signaling were found between SOX11- and SOX11+ BL cells. However, SOX11+ BL showed higher adhesion to VCAM-1 than SOX11- BL cell lines. Here we demonstrate that EBV- BL comprises two 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.

• Authors: Marta Sureda-Gómez, Ingram Iaccarino, Anna De Bolòs, Mieke Anna Meyer, Patricia Balsas, Julia Richter, Marta Leonor Rodríguez, Cristina López, Maria Carreras-Caballé, Selina Glaser, Ferran Nadeu, Pedro Jares, Maria Chiara Siciliano Dr, Cristiana Bellan, Salvatore Tornambè Dr, Roberto Boccacci Dr, Guillem Clot, Lorenzo Leoncini, Elías Campo, Reiner Siebert, Virginia Amador, Wolfram Klapper
• Journal: Blood (Blood) (Apr 15 2024) ISSN: 1528-0020 [Electronic] United States
• PMID: 38620074 (Publication Type: Journal Article)
• Copyright: Copyright © 2024 American Society of Hematology.