DNA methylation epitypes of Burkitt lymphoma with distinct molecular and clinical features Journal Article
| Authors: | Thomas, N.; García-Prieto, C. A.; Dreval, K.; Hilton, L. K.; Abramson, J. S.; Bartlett, N. L.; Bethony, J.; Bowen, J.; Bryan, A. C.; Casper, C.; Dyer, M. A.; Gastier-Foster, J. M.; Gerrie, A. S.; Greiner, T. C.; Griner, N. B.; Gross, T. G.; Harris, N.; Irvin, J. D.; Jaffe, E. S.; Leal, F. E.; Mbulaiteye, S. M.; Mullighan, C. G.; Mungall, A. J.; Mungall, K. L.; Namirembe, C.; Noy, A.; Ogwang, M. D.; Orem, J.; Ott, G.; Petrello, H.; Reynolds, S. J.; Swerdlow, S. H.; Traverse-Glehen, A.; Wilson, W. H.; Marra, M. A.; Staudt, L. M.; Scott, D. W.; Esteller, M.; Morin, R. D. |
| Article Title: | DNA methylation epitypes of Burkitt lymphoma with distinct molecular and clinical features |
| Abstract: | 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. ©2025 The Authors; |
| Keywords: | adolescent; adult; cancer survival; child; human tissue; treatment outcome; aged; middle aged; young adult; gene mutation; human cell; major clinical study; genetics; mutation; clinical feature; mortality; cancer patient; gene expression; cohort analysis; pathology; dna methylation; somatic hypermutation; epigenetics; epigenesis, genetic; molecular biology; genetic epigenesis; burkitt lymphoma; epstein barr virus; genomic dna; humans; human; male; female; article; tumor mutational burden |
| Journal Title: | Blood Cancer Discovery |
| Volume: | 6 |
| Issue: | 4 |
| ISSN: | 2643-3230 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2025-07-01 |
| Start Page: | 325 |
| End Page: | 342 |
| Language: | English |
| DOI: | 10.1158/2643-3230.Bcd-24-0240 |
| PUBMED: | 40338627 |
| PROVIDER: | scopus |
| PMCID: | PMC12209777 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
