TY - JOUR
T1 - 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
AU - Georgiadis, Panagiotis
AU - Liampa, Irene
AU - Hebels, Dennie G.
AU - Krauskopf, Julian
AU - Chatziioannou, Aristotelis
AU - Valavanis, Ioannis
AU - de Kok, Theo M. C. M.
AU - Kleinjans, Jos C. S.
AU - Bergdahl, Ingvar A.
AU - Melin, Beatrice
AU - Spaeth, Florentin
AU - Palli, Domenico
AU - Vermeulen, R. C. H.
AU - Vlaanderen, J.
AU - Chadeau-Hyam, Marc
AU - Vineis, Paolo
AU - Kyrtopoulos, Soterios A.
AU - EnviroGenomarkers Consortium
PY - 2017/9/13
Y1 - 2017/9/13
N2 - 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 <0.05) as well as 2 miRNAs (FDRConclusions: Our findings demonstrate the presence in prediagnostic blood of future CLL patients, more than 10 years before diagnosis, of CLL-like cells which evolve as preclinical disease progresses, and point to early molecular alterations with a pathogenetic potential.
AB - 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 <0.05) as well as 2 miRNAs (FDRConclusions: Our findings demonstrate the presence in prediagnostic blood of future CLL patients, more than 10 years before diagnosis, of CLL-like cells which evolve as preclinical disease progresses, and point to early molecular alterations with a pathogenetic potential.
KW - Epigenomics
KW - Transcriptomics
KW - miRNA
KW - Biomarkers of risk
KW - Molecular epidemiology
KW - Prospective cohort
KW - DISEASE PROGRESSION
KW - RISK
KW - CLL
KW - FOXP1
KW - RECEPTORS
KW - LYMPHOMAS
KW - DYNAMICS
UR - https://springernature.figshare.com/articles/dataset/Additional_file_2_Table_S1_of_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/5405740/1
U2 - 10.1186/s12864-017-4117-4
DO - 10.1186/s12864-017-4117-4
M3 - Article
C2 - 28903739
SN - 1471-2164
VL - 18
JO - BMC Genomics
JF - BMC Genomics
IS - 1
M1 - 728
ER -