PMID- 24114859
OWN - NLM
STAT- MEDLINE
DCOM- 20140602
LR  - 20240210
IS  - 1569-8041 (Electronic)
IS  - 0923-7534 (Linking)
VI  - 24
IP  - 11
DP  - 2013 Nov
TI  - Association of somatic DNA methylation variability with progression-free survival 
      and toxicity in ovarian cancer patients.
PG  - 2813-8
LID - 10.1093/annonc/mdt370 [doi]
AB  - BACKGROUND: We have addressed whether inter-individual methylation variation in 
      somatic (white blood cells, WBCs) DNA of ovarian cancer patients provides 
      potential for prognostic and/or pharmacoepigenetic stratification. PATIENTS AND 
      METHODS: WBC DNA methylation was analysed by bisulphite pyrosequencing at ataxia 
      telangiectasia mutated (ATM), estrogen receptor 1 (ESR1), progesterone receptor 
      (PGR), mutL homologue 1 (MLH1), breast cancer susceptibility gene (BRCA1), 
      secreted frizzled-related protein 1 (SFRP1), stratifin (SFN), retinoic acid 
      receptor beta (RARB) loci and the repetitive element LINE1 in 880 SCOTROC1 trial 
      patients [paclitaxel (Taxol)-carboplatin versus docetaxel (Taxotere)-carboplatin 
      as primary chemotherapy for stage Ic-IV epithelial ovarian cancer]. RESULTS: We 
      observed no significant associations (P < 0.005, after correction for multiple 
      testing) for progression-free survival (PFS) using test and validation sets. 
      However, we did identify mean SFN methylation associated with PFS (hazard ratio, 
      HR = 1.01 per 1% increase in methylation, q = 0.028); particularly in the 
      paclitaxel (HR = 1.01, q = 0.006), but not in the docetaxel arm in stratified 
      analyses. Furthermore, higher methylation within the ESR1 gene was associated 
      with CA125 response (odds ratio, OR = 1.06, q = 0.04) and with neuropathy (HR = 
      0.95, q = 0.002), but only in the paclitaxel arm of the trial. CONCLUSIONS: This 
      is the first study linking DNA methylation variability in WBC to clinical 
      outcomes for any tumour type; the data generated on novel prognostic and 
      pharmacoepigenetic DNA methylation biomarkers in the circulation now need 
      independent further evaluation.
FAU - Flanagan, J M
AU  - Flanagan JM
AD  - Epigenetics Unit, Department of Surgery and Cancer, Ovarian Cancer Action 
      Research Centre, Imperial College London, London.
FAU - Wilhelm-Benartzi, C S
AU  - Wilhelm-Benartzi CS
FAU - Metcalf, M
AU  - Metcalf M
FAU - Kaye, S B
AU  - Kaye SB
FAU - Brown, R
AU  - Brown R
LA  - eng
GR  - 13086/CRUK_/Cancer Research UK/United Kingdom
GR  - 15954/CRUK_/Cancer Research UK/United Kingdom
GR  - A11730/CRUK_/Cancer Research UK/United Kingdom
GR  - A6689/CRUK_/Cancer Research UK/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131010
PL  - England
TA  - Ann Oncol
JT  - Annals of oncology : official journal of the European Society for Medical 
      Oncology
JID - 9007735
RN  - 0 (Biomarkers, Tumor)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Biomarkers, Tumor/*genetics
MH  - Clinical Trials as Topic
MH  - CpG Islands/genetics
MH  - DNA Methylation/*genetics
MH  - Disease-Free Survival
MH  - Female
MH  - Humans
MH  - Leukocytes
MH  - Middle Aged
MH  - Ovarian Neoplasms/*drug therapy/*genetics/pathology
MH  - Paclitaxel/administration & dosage
MH  - Treatment Outcome
OTO - NOTNLM
OT  - DNA methylation
OT  - clinical trial
OT  - ovarian cancer
OT  - pharmacoepigenetics
OT  - prognosis
OT  - toxicity
EDAT- 2013/10/12 06:00
MHDA- 2014/06/03 06:00
CRDT- 2013/10/12 06:00
PHST- 2013/10/12 06:00 [entrez]
PHST- 2013/10/12 06:00 [pubmed]
PHST- 2014/06/03 06:00 [medline]
AID - S0923-7534(19)37369-7 [pii]
AID - 10.1093/annonc/mdt370 [doi]
PST - ppublish
SO  - Ann Oncol. 2013 Nov;24(11):2813-8. doi: 10.1093/annonc/mdt370. Epub 2013 Oct 10.