TY - JOUR
T1 - DNA Methylation Epitypes of Burkitt Lymphoma with Distinct Molecular and Clinical Features
AU - Thomas, Nicole
AU - García-Prieto, Carlos A.
AU - Dreval, Kostiantyn
AU - Hilton, Laura K.
AU - Abramson, Jeremy S.
AU - Bartlett, Nancy L.
AU - Bethony, Jeffrey
AU - Bowen, Jay
AU - Bryan, Anthony C.
AU - Casper, Corey
AU - Dyer, Maureen A.
AU - Gastier-Foster, Julie M.
AU - Gerrie, Alina S.
AU - Greiner, Timothy C.
AU - Griner, Nicholas B.
AU - Gross, Thomas G.
AU - Harris, Nancy
AU - Irvin, John D.
AU - Jaffe, Elaine S.
AU - Leal, Fabio E.
AU - Mbulaiteye, Sam M.
AU - Mullighan, Charles G.
AU - Mungall, Andrew J.
AU - Mungall, Karen L.
AU - Namirembe, Constance
AU - Noy, Ariela
AU - Ogwang, Martin D.
AU - Orem, Jackson
AU - Ott, German
AU - Petrello, Hilary
AU - Reynolds, Steven J.
AU - Swerdlow, Steven H.
AU - Traverse-Glehen, Alexandra
AU - Wilson, Wyndham H.
AU - Marra, Marco A.
AU - Staudt, Louis M.
AU - Scott, David W.
AU - Esteller, Manel
AU - Morin, Ryan D.
N1 - Publisher Copyright:
©2025 The Authors;
PY - 2025/7/1
Y1 - 2025/7/1
N2 - The genetic subtypes of Burkitt lymphoma have been defined, but the role of epigenetics remains to be comprehensively characterized. We searched genomic DNA from 218 patients across four continents for recurrent DNA methylation patterns and their associations with clinical and molecular features. We identified DNA methylation patterns that were not fully explained by the Epstein–Barr virus status or mutation status, leading to two epitypes described here as HypoBL and HyperBL. Each is characterized by distinct genomic and clinical features including global methylation, mutation burden, aberrant somatic hypermutation, and survival outcomes. Methylation, gene expression, and mutational differences between the epitypes support a model in which each arises from a distinct cell of origin. These results, pending validation in external cohorts, point to a refined risk assessment for patients with Burkitt lymphoma who may experience inferior outcomes. SigNiFiCANCE: Burkitt lymphoma can be divided into two epigenetic subtypes (epitypes), each carrying distinct biological, transcriptomic, genomic, and clinical features. Epitype is more strongly associated with clinical and mutational features than the Epstein–Barr virus status or genetic subtype, highlighting an important additional layer of Burkitt lymphoma pathogenesis.
AB - The genetic subtypes of Burkitt lymphoma have been defined, but the role of epigenetics remains to be comprehensively characterized. We searched genomic DNA from 218 patients across four continents for recurrent DNA methylation patterns and their associations with clinical and molecular features. We identified DNA methylation patterns that were not fully explained by the Epstein–Barr virus status or mutation status, leading to two epitypes described here as HypoBL and HyperBL. Each is characterized by distinct genomic and clinical features including global methylation, mutation burden, aberrant somatic hypermutation, and survival outcomes. Methylation, gene expression, and mutational differences between the epitypes support a model in which each arises from a distinct cell of origin. These results, pending validation in external cohorts, point to a refined risk assessment for patients with Burkitt lymphoma who may experience inferior outcomes. SigNiFiCANCE: Burkitt lymphoma can be divided into two epigenetic subtypes (epitypes), each carrying distinct biological, transcriptomic, genomic, and clinical features. Epitype is more strongly associated with clinical and mutational features than the Epstein–Barr virus status or genetic subtype, highlighting an important additional layer of Burkitt lymphoma pathogenesis.
UR - https://www.scopus.com/pages/publications/105010182285
U2 - 10.1158/2643-3230.BCD-24-0240
DO - 10.1158/2643-3230.BCD-24-0240
M3 - Article
C2 - 40338627
AN - SCOPUS:105010182285
SN - 2643-3230
VL - 6
SP - 325
EP - 342
JO - Blood cancer discovery
JF - Blood cancer discovery
IS - 4
ER -