Imperial College London
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DR JAMES M. FLANAGAN

Faculty of Medicine, Department of Surgery & Cancer

Reader in Epigenetics
 
 
 
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Contact

 

+44 (0)20 7594 2127j.flanagan

 
 
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Location

 

Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Lubecka:2018:10.1080/15592294.2018.1481706,
author = {Lubecka, K and Flower, K and Beetch, M and Qiu, J and Kurzava, L and Buvala, H and Ruhayel, A and Gawrieh, S and Liangpunsakul, S and Gonzalez, T and McCabe, G and Chalasani, N and Flanagan, JM and Stefanska, B},
doi = {10.1080/15592294.2018.1481706},
journal = {Epigenetics},
pages = {605--626},
title = {Loci-specific differences in blood DNA methylation in HBV-negative populations at risk for hepatocellular carcinoma development},
url = {http://dx.doi.org/10.1080/15592294.2018.1481706},
volume = {13},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Late onset of clinical symptoms in hepatocellular carcinoma (HCC) results in late diagnosis and poor disease outcome. Approximately 85% of individuals with HCC have underlying liver cirrhosis. However, not all cirrhotic patients develop cancer. Reliable tools that would distinguish cirrhotic patients who will develop cancer from those who will not are urgently needed. We used the Illumina HumanMethylation450 BeadChip microarray to test whether white blood cell DNA, an easily accessible source of DNA, exhibits site-specific changes in DNA methylation in blood of diagnosed HCC patients (post-diagnostic, 24 cases, 24 controls) and in prospectively collected blood specimens of HCC patients who were cancer-free at blood collection (pre-diagnostic, 21 cases, 21 controls). Out of 22 differentially methylated loci selected for validation by pyrosequencing, 19 loci with neighbouring CpG sites (probes) were confirmed in the pre-diagnostic study group and subjected to verification in a prospective cirrhotic cohort (13 cases, 23 controls). We established for the first time 9 probes that could distinguish HBV-negative cirrhotic patients who subsequently developed HCC from those who stayed cancer-free. These probes were identified within regulatory regions of BARD1, MAGEB3, BRUNOL5, FXYD6, TET1, TSPAN5, DPPA5, KIAA1210, and LSP1. Methylation levels within DPPA5, KIAA1210, and LSP1 were higher in prospective samples from HCC cases versus cirrhotic controls. The remaining probes were hypomethylated in cases compared with controls. Using blood as a minimally invasive material and pyrosequencing as a straightforward quantitative method, the established probes have potential to be developed into a routine clinical test after validation in larger cohorts.
AU  - Lubecka,K
AU  - Flower,K
AU  - Beetch,M
AU  - Qiu,J
AU  - Kurzava,L
AU  - Buvala,H
AU  - Ruhayel,A
AU  - Gawrieh,S
AU  - Liangpunsakul,S
AU  - Gonzalez,T
AU  - McCabe,G
AU  - Chalasani,N
AU  - Flanagan,JM
AU  - Stefanska,B
DO  - 10.1080/15592294.2018.1481706
EP  - 626
PY  - 2018///
SN  - 1559-2294
SP  - 605
TI  - Loci-specific differences in blood DNA methylation in HBV-negative populations at risk for hepatocellular carcinoma development
T2  - Epigenetics
UR  - http://dx.doi.org/10.1080/15592294.2018.1481706
UR  - https://www.ncbi.nlm.nih.gov/pubmed/29927686
UR  - http://hdl.handle.net/10044/1/61049
VL  - 13
ER  -
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