MYC-rearranged mature B-cell lymphomas in children and young adults are molecularly Burkitt Lymphoma
Sara Mato, Natalia Castrejón de Anta, Ariadna Colmenero, Lorenzo Carità, Julia Salmerón‐Villalobos, Joan E. Ramis-Zaldivar, Ferran Nadeu, Noelia García Barrio, Luojun Wang, Jaime Verdú‐Amorós, Mara Andrés, Núria Conde, Verónica Celis, Maria José Ortega, A. Galera, Itziar Astigarraga, Vanesa Pérez‐Alonso, Eduardo Quiroga, Aixiang Jiang, David W. Scott, Elı́as Campo, Olga Balagué, Itziar Salaverría
Abstract
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.