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Table 1 A summary of aberrant DNA methylation associated with outcome in breast cancer

From: Epigenome remodelling in breast cancer: insights from an early in vitro model of carcinogenesis

Gene symbol Tissue type Hyper/Hypo Cohort size Detection method Association with prognosis Pvalue Hazard ratioa Reference
ACADL NR Hyper 59 ductal carcinomas, 24 matched normal IA/CoBRA Reduced relapse-free survival 0.0001   [50]
BMP4 FF Hyper 241 patients with breast cancer MethyLight Reduced time to distant metastasis 0.0002   [51]
BRCA1 FFPE Hyper 536 tumors (Chinese patients) MSP Reduced disease-free survival 0.045 1.45 [52]
      Reduced disease-specific survival 0.038 1.56  
  FF Hyper 241 patients with breast cancer MethyLight Reduced time to distant metastasis 0.018   [51]
  Serum Hyper 105 tumors, 20 unmatched normal MSP Poor prognosis 0.002 6.4 [53]
  FF Hyper 82 primary breast cancer tissues (Tunisian cohort) MSP Five-year survival 0.016   [54]
BRCA1 or P16 or both Serum Hyper 105 tumors, 20 unmatched normal MSP Poor prognosis 0.002 10.7 [53]
C20ORF55 FF Hyper 241 patients with breast cancer MethyLight Reduced time to distant metastasis 0.001   [51]
CDO1 FF Hyper 163 tumors, 64 with distant metastasis Q-BSSeq Reduced time to distant metastasis <0.0128 >3.5 [55]
      Reduced metastasis-free survival <0.0034   
CIDEB FF Hyper 110 tumors, 11 normal (Indian cohort) MOMA Increased likelihood of relapse 0.002 4.02 [56]
CST6 FFPE Hyper 93 carcinomas, 10 carcinomas with adjacent normal, 10 fibroadenomas, and 11 normal MSP Reduced disease-free interval Reduced overall survival 0.004 0.001   [57]
      Reduced disease-free interval 0.027 3.48  
      Reduced overall survival 0.004 9.19  
DKK3 FF Hyper 153 primary invasive cancers, 19 normal MSP Reduced overall survival 0.011 14.4 [58]
      Reduced disease-free survival 0.047 2.5  
ELK1 FF Hyper 130 tumors, 11 normal (Indian cohort) MOMA Increased likelihood of relapse 0.005 3.53 [56]
ESR2 (ER-B) FF Hyper 55 cancers MSP Increased incidence of relapse 0.016   [59]
FGF12 FF Hyper 113 tumors, 11 normal (Indian cohort) MOMA Increased likelihood of relapse 0.004 3.31 [56]
FGF4 FF Hyper 241 patients with breast cancer MethyLight Reduced time to distant metastasis 0.029   [51]
FOXH1 FF Hyper 129 tumors, 11 normal (Indian cohort) MOMA Increased likelihood of relapse 0.00007 5.09 [56]
FOXL2 FF Hyper 241 patients with breast cancer MethyLight Reduced time to distant metastasis 0.02   [51]
GSTP1 FF Hyper 176 invasive tumors (Japanese cohort) MSP Reduced relapse-free survival <0.01   [60]
      Poor prognosis <0.05 2.77  
      Poor prognosis <0.01 7.13  
  FFPE Hyper 974 primary in situ or invasive breast cancers MethyLight Increased breast cancer-specific mortality NR 1.71 [61]
  FFPE Hyper 50 breast tumors MSP High Nottingham Prognostic Index 0.0017   [62]
HOXB13 FF Hyper 57 ER-α+ tumors QM-PCR Reduced disease-free survival 0.029 3.25 [36]
ID4 FF Hyper 171 tumors and match normal MSP Reduced recurrence-free survival 0.036   [63]
ITIH5 FF Hyper 109 tumors MSP Reduced overall survival 0.008   [64]
ITR NR Hyper 59 ductal carcinomas, 24 matched normal IA/CoBRA Reduced relapse-free survival 0.0041   [50]
KLK10 FFPE Hyper 128 breast carcinomas, 10 breast carcinomas with paired adjacent normal, 10 breast fibroadenomas, and 11 normal MSP Reduced disease-free interval Reduced overall survival Increased incidence of relapse 0.0025
0.003
0.026
/
/
3.49
[65]
LHX5 FF Hyper 125 tumors, 11 normal (Indian cohort) MOMA Increased likelihood of relapse 0.032 2.94 [56]
MLH1 FF Hyper 86 primary breast cancer tissues (Tunisian cohort) MSP Reduced overall survival 0.015   [54]
NR2E1 FF Hyper 241 patients with breast cancer MethyLight Reduced time to distant metastasis 0.02   [51]
OLIG2 FF Hyper 115 tumors, 11 normal (Indian cohort) MOMA Increased likelihood of relapse 0.023 2.56 [56]
ONECUT1 FF Hyper 128 tumors, 11 normal (Indian cohort) MOMA Increased likelihood of relapse 0.023 2.8 [56]
P16 Serum Hyper 105 tumors, 20 unmatched normal MSP Poor prognosis 0.001 5.5 [53]
PITX2 FFPE Hyper 427 invasive cancers QM-PCR Reduced time to distant metastasis 0.004 2.75 [66]
      Reduced time to distant metastasis 0.013 2.35  
      Reduced metastasis-free survival 0.032 2.69  
  FF Hyper 241 patients with breast cancer MethyLight High risk of distant recurrence 0.026   [51]
      Reduced time to distant metastasis <0.001   
      Reduced disease-free survival 0.0084   
      Reduced overall survival 0.0003   
  FF Hyper 236 node-negative tumors Array/QM-PCR Reduced metastasis-free survival <0.00045 >2.1 [67]
  FF Hyper 416 tumors QM-PCR Reduced time to distant metastasis <0.01 1.71 [68]
      Reduced overall survival <0.01 1.71  
      Reduced metastasis-free survival <0.01 1.74  
      Reduced overall survival 0.02 1.46  
PITX2/BMP4/c20orf55/fgf5 FF Hyper 241 patients with breast cancer MethyLight Increased risk of distant recurrence Increased risk of distant recurrence <0.01
<0.01
  [51]
RARB FFPE Hyper 967 primary in situ or invasive breast cancers MethyLight Increased breast cancer-specific mortality NR 1.78 [61]
RASSF1A FF Hyper 80 tumors (Tunisian cohort) MSP Poor survival 0.014   [69]
  FFPE Hyper 93 carcinomas, 10 carcinomas with adjacent normal, 10 fibroadenomas, and 11 normal MSP Increased incidence of relapse Reduced disease-free survival 0.011
0.028
  [70]
  FNA Hyper 237 patients with suspicious palpable lesions taken prior to surgery QM-PCR Reduced disease-free survival 0.031 OR = 2.53 [71]
RECK NR Hyper 59 ductal carcinomas, 24 matched normal IA/CoBRA Reduced relapse-free survival 0.0001   [50]
SFRP1 FF Hyper 131 tumors, 26 matched normal MSP Reduced overall survival 0.045   [46]
SFRP2 NR Hyper 59 ductal carcinomas, 24 matched normal IA/CoBRA Reduced relapse-free survival 0.0001   [50]
SFRP5 FF Hyper 14 matched tumors and normal, 155 unmatched tumors MSP Reduced overall survival 0.049 4.55 [72]
SYNM FF/FFPE Hyper 195 breast cancers MSP Reduced recurrence-free survival 0.0282 2.94 [73]
TDGF1 FF Hyper 109 tumors, 11 normal (Indian cohort) MOMA Increased likelihood of relapse 0.0009 4.08 [56]
TLX3 FF Hyper 241 patients with breast cancer MethyLight Reduced time to distant metastasis 0.008   [51]
TUBB3 FF Hyper 121 tumors, 11 normal (Indian cohort) MOMA Increased likelihood of relapse 0.035 3.19 [56]
TWIST1 FFPE Hyper 973 primary in situ or invasive breast cancers MethyLight Increased breast cancer-specific mortality NR 1.67 [61]
UAP1L1 NR Hyper 59 ductal carcinomas, 24 matched normal IA/CoBRA Reduced relapse-free survival 0.0005   [50]
UGT3A1 NR Hyper 59 ductal carcinomas, 24 matched normal IA/CoBRA Reduced relapse-free survival 0.0018   [50]
UNC5A FF Hyper 111 tumors, 11 normal (Indian cohort) MOMA Increased likelihood of relapse 0.027 2.74 [56]
ZNF1A1 FF Hyper 241 patients with breast cancer MethyLight Reduced time to distant metastasis 0.044   [51]
BTG1 FF Hypo 124 tumors, 11 normal (Indian cohort) MOMA Increased likelihood of relapse 0.013 2.65 [56]
GSC FF Hypo 132 tumors, 11 normal (Indian cohort) MOMA Increased likelihood of relapse 0.002 3.69 [56]
HDAC4 FF Hypo 117 tumors, 11 normal (Indian cohort) MOMA Increased likelihood of relapse 0.016 2.62 [56]
JUN FF Hypo 131 tumors, 11 normal (Indian cohort) MOMA Increased likelihood of relapse 0.025 2.44 [56]
MKI67 (KI-67) FF Hypo 116 tumors, 11 normal (Indian cohort) MOMA Increased likelihood of relapse 0.004 3.43 [56]
KIF2C FF Hypo 118 tumors, 11 normal (Indian cohort) MOMA Increased likelihood of relapse 0.008 2.65 [56]
KLF4 FF Hypo 114 tumors, 11 normal (Indian cohort) MOMA Increased likelihood of relapse 0.009 2.63 [56]
KLF5 FF Hypo 123 tumors, 11 normal (Indian cohort) MOMA Increased likelihood of relapse 0.004 3.56 [56]
LHX2 FF Hypo 126 tumors, 11 normal (Indian cohort) MOMA Increased likelihood of relapse 0.028 2.32 [56]
MAPK12 FF Hypo 120 tumors, 11 normal (Indian cohort) MOMA Increased likelihood of relapse 0.001 3.51 [56]
MRD1 FF/serum Hypo 100 invasive ductal carcinomas with matched normal and blood MSP Reduced overall survival <0.01   [74]
ONECUT2 FF Hypo 127 tumors, 11 normal (Indian cohort) MOMA Increased likelihood of relapse 0.029 2.74 [56]
SPRY1 FF Hypo 112 tumors, 11 normal (Indian cohort) MOMA Increased likelihood of relapse 0.002 4.0 [56]
TOP1 FF Hypo 108 tumors, 11 normal (Indian cohort) MOMA Increased likelihood of relapse 0.0005 3.68 [56]
UBE2C FF Hypo 119 tumors, 11 normal (Indian cohort) MOMA Increased likelihood of relapse 0.0009 3.57 [56]
VEGF FF Hypo 122 tumors, 11 normal (Indian cohort) MOMA Increased likelihood of relapse 0.007 3.01 [56]
  1. aHazard ratio given where reported. FF, fresh frozen; FFPE, formalin-fixed paraffin-embedded; FNA, fine-needle aspirate; HR, hazard ratio; Hyper, hypermethylation; Hypo, hypomethylation; IA/CoBRA, infinium array/combined bisulfite restriction enzyme analysis; MOMA, methylation oligonucleotide analysis; MSP, methylation-specific polymerase chain reaction; NR, not reported; OR, odds ratio; Q-BSSeq, quantitative bisulphite sequencing; QM-PCR, quantitative methylation-specific polymerase chain reaction.