Imperial College London

DrJayChatterjee

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Honorary Clinical Senior Lecturer
 
 
 
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Contact

 

j.chatterjee

 
 
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Location

 

Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Phelps:2017:10.1038/bjc.2017.83,
author = {Phelps, DL and Borley, J and Flower, K and Dina, R and Darb-Esfahani, S and Braicu, I and Sehouli, J and Fotopoulou, C and Wilhelm-Benartzi, CS and Gabra, H and Yazbek, J and Chatterjee, J and Ip, J and Khan, H and Likos-Corbett, MT and Brown, R and Ghaem-Maghami, S},
doi = {10.1038/bjc.2017.83},
journal = {British Journal of Cancer},
pages = {1287--1293},
title = {Methylation of MYLK3 gene promoter region: a biomarker to stratify surgical care in ovarian cancer in a multi-centre study},
url = {http://dx.doi.org/10.1038/bjc.2017.83},
volume = {116},
year = {2017}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - BackgroundSurvival benefit from surgical debulking of ovarian cancer (OC) is well established but some women, despite total macroscopic clearance of disease, still have poor prognosis. We aimed to identify biomarkers to predict benefit from conventional surgery.MethodsClinical data from women debulked for high-stage OC was analysed (Hammersmith Hospital, London, UK; 2001-2014). Infinium’s HumanMethylation27 array interrogated tumour-DNA for differentially-methylated CpG sites, correlated to survival, in patients with the least residual disease (RD) (Hammersmith Array). Validation was performed using bisulphite pyrosequencing (Charité Hospital, Berlin, Germany cohort) and The Cancer Genome Atlas’ (TCGA) methylation dataset. Kaplan-Meier curves and Cox models tested survival.ResultsAltogether 803 women with serous ovarian cancer were studied. No RD was associated with significantly improved overall- (OS) (hazard ratio [HR] 1.25, 95% CI 1.06-1.47; P=0.0076) and progression-free survival (PFS) (HR 1.23, 1.05-1.43; P=0.012) (Hammersmith database n=430). Differentially-methylated loci within FGF4, FGF21, MYLK2, MYLK3, MYL7, and ITGAE associated with survival. Patients with the least RD had significantly better OS with higher methylation of MYLK3 (Hammersmith (HR 0.51, 0.31-0.84; P=0.01), Charité (0.46, 0.21-1.01; P=0.05), TCGA (0.64, 0.44-0.93; P=0.02)). ConclusionMYLK3 methylation is associated with improved OS in patients with the least RD, which could potentially be used to determine response to surgery.
AU - Phelps,DL
AU - Borley,J
AU - Flower,K
AU - Dina,R
AU - Darb-Esfahani,S
AU - Braicu,I
AU - Sehouli,J
AU - Fotopoulou,C
AU - Wilhelm-Benartzi,CS
AU - Gabra,H
AU - Yazbek,J
AU - Chatterjee,J
AU - Ip,J
AU - Khan,H
AU - Likos-Corbett,MT
AU - Brown,R
AU - Ghaem-Maghami,S
DO - 10.1038/bjc.2017.83
EP - 1293
PY - 2017///
SN - 1532-1827
SP - 1287
TI - Methylation of MYLK3 gene promoter region: a biomarker to stratify surgical care in ovarian cancer in a multi-centre study
T2 - British Journal of Cancer
UR - http://dx.doi.org/10.1038/bjc.2017.83
UR - http://hdl.handle.net/10044/1/45456
VL - 116
ER -