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| Status |
Public on Mar 26, 2025 |
| Title |
DNA methylation epitypes of Burkitt lymphoma with distinct molecular and clinical features |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by genome tiling array
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| Summary |
The genetic drivers of Burkitt Lymphoma (BL) have been comprehensively explored while the role of epigenetics remains unclear. Using samples from patients across four continents, we searched for sites with consistent DNA methylation changes and associations with clinical and molecular features such as Epstein-Barr virus (EBV) status and driver mutations. We identified robust methylation patterns that were not fully explained by EBV status, implying the existence of robust epitypes: HypoBL and HyperBL. The latter had distinct genomic and clinical features including global hypermethylation, a higher mutation burden, elevated aberrant somatic hypermutation, and inferior 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 suggest an approach for identifying BL patients with a greater risk of treatment failure and provide a basis for the exploration of new therapeutic strategies that target the unique molecular underpinnings of each group.
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| Overall design |
Cases were accrued within the Burkitt Lymphoma Genome Sequencing Project (BLGSP) from the following sites: Uganda Cancer Institute (UCI, Uganda), Epidemiology of Burkitt’s Lymphoma in East-African Children and Minors (EMBLEM) study, at St. Mary’s Hospital, Lacor, Uganda), Children’s Oncology Group (COG, USA) sites that participated in the AALL1131 clinical trial, St. Jude Children’s Research Hospital (USA), Memorial Sloan Kettering Cancer Center (USA), Massachusetts General Hospital (USA), Belo Horizonte (Brazil), Lyon University Hospital (France), Washington University in St. Louis (USA), National Cancer Institute (USA), BC Cancer (Canada), and Robert-Bosch-Krankenhaus (Germany). Patients at the age of enrollment older than 20 years were considered adults for the purpose of this study. The study data set consisted of pediatric and adult BL patients. A total of 218 BL samples and 6 normal centroblast samples were preserved for further analysis. Additionally, 13 BL cell lines were also profiled.
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| Contributor(s) |
Thomas N, Garcia-Prieto CA, Dreval K, Hilton LK, Abramson JS, Bartlett NL, Bethony J, Bowen J, Bryan AC, Casper C, Dyer MA, Gastier-Foster JM, Gerrie AS, Greiner TC, Griner NB, Gross TG, Harris NL, Irvin JD, Jaffe ES, Leal F, Mbulaiteye SM, Mullighan CG, Mungall AJ, Mungall K, Namirembe C, Noy A, Ogwang MD, Orem J, Ott G, Petrello H, Reynolds SJ, Swerdlow SH, Traverse-Glehen A, Wilson WH, Marra MA, Staudt LM, Scott DW, Esteller M, Morin RD |
| Citation missing |
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| Submission date |
Mar 23, 2025 |
| Last update date |
Mar 26, 2025 |
| Contact name |
Ryan D. Morin |
| Organization name |
Simon Fraser University
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| Department |
Molecular Biology and Biochemistry
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| Lab |
Ryan Morin Lab
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| Street address |
8888 University Drive
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| City |
Burnaby |
| State/province |
BC |
| ZIP/Postal code |
V5A 1S6 |
| Country |
Canada |
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| Platforms (1) |
| GPL23976 |
Illumina Infinium HumanMethylation850 BeadChip |
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