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The proliferative history shapes the DNA methylome of B-cell tumors and predicts clinical outcome

Authors
 Martí Duran-Ferrer  ;  Guillem Clot  ;  Ferran Nadeu  ;  Renée Beekman  ;  Tycho Baumann  ;  Jessica Nordlund  ;  Yanara Marincevic-Zuniga  ;  Gudmar Lönnerholm  ;  Alfredo Rivas-Delgado  ;  Silvia Martin  ;  Raquel Ordoñez  ;  Giancarlo Castellano  ;  Marta Kulis  ;  Ana Queirós  ;  Lee Seung-Tae  ;  Joseph Wiemels  ;  Romina Royo  ;  Montserrat Puiggrós  ;  Junyan Lu  ;  Eva Gine  ;  Sílvia Beà  ;  Pedro Jares  ;  Xabier Agirre  ;  Felipe Prosper  ;  Carlos López-Otín  ;  Xosé S Puente  ;  Christopher C Oakes  ;  Thorsten Zenz  ;  Julio Delgado  ;  Armando López-Guillermo  ;  Elías Campo  ;  José Ignacio Martin-Subero 
Citation
 NATURE CANCER, Vol.1(11) : 1066-1081, 2020-11 
Journal Title
NATURE CANCER
ISSN
 2662-1347 
Issue Date
2020-11
Abstract
We report a systematic analysis of the DNA methylation variability in 1,595 samples of normal cell subpopulations and 14 tumor subtypes spanning the entire human B-cell lineage. Differential methylation among tumor entities relates to differences in cellular origin and to de novo epigenetic alterations, which allowed us to build an accurate machine learning-based diagnostic algorithm. We identify extensive patient-specific methylation variability in silenced chromatin associated with the proliferative history of normal and neoplastic B cells. Mitotic activity generally leaves both hyper- and hypomethylation imprints, but some B-cell neoplasms preferentially gain or lose DNA methylation. Subsequently, we construct a DNA methylation-based mitotic clock called epiCMIT, whose lapse magnitude represents a strong independent prognostic variable in B-cell tumors and is associated with particular driver genetic alterations. Our findings reveal DNA methylation as a holistic tracer of B-cell tumor developmental history, with implications in the differential diagnosis and prediction of clinical outcome.
Files in This Item:
T999202305.pdf Download
DOI
10.1038/s43018-020-00131-2
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
Yonsei Authors
Lee, Seung-Tae(이승태) ORCID logo https://orcid.org/0000-0003-1047-1415
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/185001
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