학술논문
Evolving DNA methylation and gene expression markers of B-cell chronic lymphocytic leukemia are present in pre-diagnostic blood samples more than 10 years prior to diagnosis
Document Type
article
Author
Panagiotis Georgiadis; Irene Liampa; Dennie G. Hebels; Julian Krauskopf; Aristotelis Chatziioannou; Ioannis Valavanis; Theo M.C.M. de Kok; Jos C.S. Kleinjans; Ingvar A. Bergdahl; Beatrice Melin; Florentin Spaeth; Domenico Palli; R.C.H. Vermeulen; J. Vlaanderen; Marc Chadeau-Hyam; Paolo Vineis; Soterios A. Kyrtopoulos; on behalf of the EnviroGenomarkers consortium
Source
BMC Genomics, Vol 18, Iss 1, Pp 1-15 (2017)
Subject
Language
English
ISSN
1471-2164
Abstract
Abstract Background B-cell chronic lymphocytic leukemia (CLL) is a common type of adult leukemia. It often follows an indolent course and is preceded by monoclonal B-cell lymphocytosis, an asymptomatic condition, however it is not known what causes subjects with this condition to progress to CLL. Hence the discovery of prediagnostic markers has the potential to improve the identification of subjects likely to develop CLL and may also provide insights into the pathogenesis of the disease of potential clinical relevance. Results We employed peripheral blood buffy coats of 347 apparently healthy subjects, of whom 28 were diagnosed with CLL 2.0–15.7 years after enrollment, to derive for the first time genome-wide DNA methylation, as well as gene and miRNA expression, profiles associated with the risk of future disease. After adjustment for white blood cell composition, we identified 722 differentially methylated CpG sites and 15 differentially expressed genes (Bonferroni-corrected p