Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	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
Δημιουργός/Συγγραφέας:	[EL] Γεωργιάδης, Παναγιώτης[EN] Georgiadis, Panagiotis Liampa I. Hebels D.G. Krauskopf J. [EL] Χατζηιωάννου, Αριστοτέλης[EN] Chatziioannou, Aristotelis Valavanis I. de Kok T.M.C.M. Kleinjans J.C.S. Bergdahl I.A. Melin B. Spaeth F. Palli D. Vermeulen R.C.H. Vlaanderen J. Chadeau-Hyam M. Vineis P. [EL] Κυρτόπουλος, Σωτήριος Α.[EN] Kyrtopoulos, Soterios A. Gottschalk R. van Leeuwen D. Timmermans L. Botsivali M. Bendinelli B. Kelly R. Portengen L. Saberi-Hosnijeh F. Hallmans G. Lenner P. Keun H.C. Siskos A. Athersuch T.J. Kogevinas M. Stephanou E.G. Myridakis A. Fazzo L. Santis M.D. Comba P. Kiviranta H. Rantakokko P. Airaksinen R. Ruokojärvi P. Gilthorpe M. Fleming S. Fleming T. Tu Y.-K. Jonsson B. Lundh T. Chen W.J. Lee W.-C. Hsiao C.K. Chien K.-L. Kuo P.-H. Hung H. Liao S.-F. on behalf of the EnviroGenomarkers consortium
Εκδότης:	BioMed Central Ltd.
Ημερομηνία:	2017
Γλώσσα:	Αγγλικά
ISSN:	1471-2164
DOI:	10.1186/s12864-017-4117-4
Άλλο:	PubMed ID: 28903739
Περίληψη:	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 (FDR < 0.05) which were associated with the risk of future CLL. The majority of these signals have also been observed in clinical CLL, suggesting the presence in prediagnostic blood of CLL-like cells. Future CLL cases who, at enrollment, had a relatively low B-cell fraction (<10%), and were therefore less likely to have been suffering from undiagnosed CLL or a precursor condition, showed profiles involving smaller numbers of the same differential signals with intensities, after adjusting for B-cell content, generally smaller than those observed in the full set of cases. A similar picture was obtained when the differential profiles of cases with time-to-diagnosis above the overall median period of 7.4 years were compared with those with shorted time-to-disease. Differentially methylated genes of major functional significance include numerous genes that encode for transcription factors, especially members of the homeobox family, while differentially expressed genes include, among others, multiple genes related to WNT signaling as well as the miRNAs miR-150-5p and miR-155-5p. Conclusions: 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.
Τίτλος πηγής δημοσίευσης:	BMC Genomics
Τόμος/Κεφάλαιο:	18
Τεύχος:	1
Θεματική Κατηγορία:	[EL] Βιολογία (Γενικά)[EN] Biology (General)
Λέξεις-Κλειδιά:	Biomarkers of risk Epigenomics MiRNA Molecular epidemiology Prospective cohort Transcriptomics
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
Κάτοχος πνευματικών δικαιωμάτων:	© 2017 The Author(s).
Όροι και προϋποθέσεις δικαιωμάτων:	All Open Access, Gold, Green
Σημειώσεις:	Seventh Framework Programme, FP7: 226756; European Commission, EC
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο