MYC-rearranged mature B-cell lymphomas in children and young adults are molecularly Burkitt Lymphoma
Aggressive B-cell non-Hodgkin lymphomas (NHL) in children, adolescents, and young adults (CAYA) include Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), and a subset of high-grade tumors with features intermediate between these entities whose genetic and molecular profiles have not been completely elucidated. In this study, we have characterized 37 aggressive B-NHL in CAYA, 33 with high-grade morphology, and 4 DLBCL with MYC rearrangement (MYC-R), using targeted next-generation sequencing and the aggressive lymphoma gene expression germinal center B-cell-like (GCB), activated B-cell-like (ABC), and dark zone signatures (DZsig). Twenty-two tumors had MYC-R without BCL2 breaks, and two MYC-non-R cases had BCL6 translocations. MYC-R cases, including DLBCL, carried BL-related mutations and copy number alterations. Conversely, MYC-non-R lymphomas had alterations in the B-cell receptor signaling/NF-κB pathway (71%). DZsig was expressed in 12/13 of MYC-R tumors but only in 2/10 of MYC-non-R GCB tumors (P < 0.001). The 3-year event-free survival (EFS) of the whole cohort was 79.6%. TP53 and KMT2C mutations conferred inferior outcome (3-year EFS P < 0.05). Overall, MYC-R lymphomas in CAYA have a molecular profile similar to BL regardless of their high-grade or DLBCL morphology, whereas MYC-non-R has more heterogeneous genetic alterations closer to that of DLBCL.
Authors
- Verónica Celis (ORCID: https://orcid.org/0009-0007-9465-0424)
- Joan E. Ramis-Zaldivar (ORCID: https://orcid.org/0000-0001-7108-7738)
- Ariadna Colmenero (ORCID: https://orcid.org/0000-0002-7966-0057)
- Jaime Verdú‐Amorós (ORCID: https://orcid.org/0000-0002-0900-0889)
- Olga Balagué (ORCID: https://orcid.org/0000-0002-5099-3675)
- Luojun Wang (ORCID: https://orcid.org/0000-0001-8226-6432)
- Aixiang Jiang (ORCID: https://orcid.org/0000-0002-6153-7595)
- David W. Scott (ORCID: https://orcid.org/0000-0002-0435-5947)
- Maria José Ortega
- Sara Mato (ORCID: https://orcid.org/0000-0001-7269-2470)
- Elı́as Campo (ORCID: https://orcid.org/0000-0001-9850-9793)
- Julia Salmerón‐Villalobos (ORCID: https://orcid.org/0000-0002-7092-9160)
- Eduardo Quiroga (ORCID: https://orcid.org/0000-0002-7651-0213)
- Itziar Astigarraga (ORCID: https://orcid.org/0000-0002-5012-0137)
- A. Galera (ORCID: https://orcid.org/0000-0002-5355-8003)
- Mara Andrés (ORCID: https://orcid.org/0000-0001-8274-5724)
- Ferran Nadeu (ORCID: https://orcid.org/0000-0003-2910-9440)
- Núria Conde
- Itziar Salaverría (ORCID: https://orcid.org/0000-0002-2427-9822)
- Natalia Castrejón de Anta (ORCID: https://orcid.org/0000-0002-0647-3058)
- Noelia García Barrio (ORCID: https://orcid.org/0000-0002-2789-8426)
- Vanesa Pérez‐Alonso
- Lorenzo Carità
Institutions
- Hospital Sant Joan de Déu Barcelona (ES)
- University of British Columbia (CA)
- Spinal Cord Injury BC (CA)
- BioCruces Health research Institute (ES)
- Hospital Universitario 12 De Octubre (ES)
- Hospital Clínic de Barcelona (ES)
- Hospital Universitario Virgen de las Nieves (ES)
- Leitat Technological Center (ES)
- Osakidetza (ES)
- Hospital Universitario Virgen de la Arrixaca (ES)
- Hospital Universitario Virgen del Rocío (ES)
- INCLIVA Health Research Institute (ES)
- Centro de Investigación Biomédica en Red de Cáncer (ES)
- Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES)
- Universitat de Barcelona (ES)
Publication Details
- Journal
- Blood Cancer Journal
- Published
- 2024-10-07
- DOI
- https://doi.org/10.1038/s41408-024-01153-0
- Citations
- 12
- Primary Topic
- Lymphoma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 5.10
Funders
- European Commission
- Generalitat de Catalunya
- Instituto de Salud Carlos III
- European Regional Development Fund
- Agencia Estatal de Investigación