Genetic and epigenetic profiling of CLL disease progression reveals limited somatic evolution and suggests a relationship to memory-cell development View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-04

AUTHORS

E N Smith, E M Ghia, C M DeBoever, L Z Rassenti, K Jepsen, K-A Yoon, H Matsui, S Rozenzhak, H Alakus, P J Shepard, Y Dai, M Khosroheidari, M Bina, K L Gunderson, K Messer, L Muthuswamy, T J Hudson, O Harismendy, C L Barrett, C H M Jamieson, D A Carson, T J Kipps, K A Frazer

ABSTRACT

We examined genetic and epigenetic changes that occur during disease progression from indolent to aggressive forms of chronic lymphocytic leukemia (CLL) using serial samples from 27 patients. Analysis of DNA mutations grouped the leukemia cases into three categories: evolving (26%), expanding (26%) and static (47%). Thus, approximately three-quarters of the CLL cases had little to no genetic subclonal evolution. However, we identified significant recurrent DNA methylation changes during progression at 4752 CpGs enriched for regions near Polycomb 2 repressive complex (PRC2) targets. Progression-associated CpGs near the PRC2 targets undergo methylation changes in the same direction during disease progression as during normal development from naive to memory B cells. Our study shows that CLL progression does not typically occur via subclonal evolution, but that certain CpG sites undergo recurrent methylation changes. Our results suggest CLL progression may involve developmental processes shared in common with the generation of normal memory B cells. More... »

PAGES

e303

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/bcj.2015.14

    DOI

    http://dx.doi.org/10.1038/bcj.2015.14

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1041187927

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25860294


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