Imperial College London
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DrAlexandrosSiskos

Faculty of Medicine, Department of Surgery & Cancer

Honorary Research Fellow
 
 
 
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Contact

 

a.siskos Website

 
 
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Location

 

Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Georgiadis:2017:10.1186/s12864-017-4117-4,
author = {Georgiadis, P and Liampa, I and Hebels, DG and Krauskopf, J and Chatziioannou, A and Valavanis, I and de, Kok TMCM and Kleinjans, JCS and Bergdahl, IA and Melin, B and Spaeth, F and Palli, D and Vermeulen, RCH and Vlaanderen, J and Chadeau-Hyam, M and Vineis, P and Kyrtopoulos, SA and EnviroGenomarkers, consortium},
doi = {10.1186/s12864-017-4117-4},
journal = {BMC Genomics},
title = {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.},
url = {http://dx.doi.org/10.1186/s12864-017-4117-4},
volume = {18},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
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 (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
AU  - Georgiadis,P
AU  - Liampa,I
AU  - Hebels,DG
AU  - Krauskopf,J
AU  - Chatziioannou,A
AU  - Valavanis,I
AU  - de,Kok TMCM
AU  - Kleinjans,JCS
AU  - Bergdahl,IA
AU  - Melin,B
AU  - Spaeth,F
AU  - Palli,D
AU  - Vermeulen,RCH
AU  - Vlaanderen,J
AU  - Chadeau-Hyam,M
AU  - Vineis,P
AU  - Kyrtopoulos,SA
AU  - EnviroGenomarkers,consortium
DO  - 10.1186/s12864-017-4117-4
PY  - 2017///
SN  - 1471-2164
TI  - 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.
T2  - BMC Genomics
UR  - http://dx.doi.org/10.1186/s12864-017-4117-4
UR  - http://hdl.handle.net/10044/1/50956
VL  - 18
ER  -
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