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Table 1 Summary of representative clinical studies performed during the period (2011–2016) to estimate global levels of DNA methylation derivatives. Abbreviations: FFPE- Archived Formalin-fixed, Paraffin-embedded; IHC- Immunohistochemistry; Liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS)

From: Technical advances in global DNA methylation analysis in human cancers

Epigenetic Mark

Method of Study

Tumor type

Observation

Clinical relevance of observation

5mC

IHC

Colorectal cancer (n = 30) Vs Control group (n = 30)

Loss of 5mC

Associated with advanced colorectal adenomatous polyps [88]

5hmC

IHC

Clear cell renal cell carcinoma (n = 111) Vs matched adjacent tissue

Loss of 5hmC

No correlation with grade/prognosis [89]

5hmC

IHC

Urothelial cell carcinoma (n = 55) Vs matched adjacent tissue

Loss of 5hmC

No correlation with grade/prognosis [89]

5mC & 5hmC

LC-ESI-MS

Clear cell renal cell carcinoma (n = 36) Vs paired normal

Loss of 5hmCNo change in 5mC

No correlation with grade/prognosis [90]

5mC

IHC

Tongue squamous cell carcinoma (TSCC) (n = 248) Vs Tumor adjacent normal (TAN) (n = 235)

Loss of 5hmC

Associated with the poor disease-specific survival in TSCC patients [91]

5mC

ELISA

Renal Cell Carcinoma (n = 889) Vs age, gender, ethnicity matched control group (n = 889)

Loss of 5mC

Associated with risk of developing RCC [92]

5mC

LINE1pyrosequencing

Hepatocellular carcinoma (n = 208)

Loss of 5mC

Associated with poor disease free survival [93]

5mC

LINE1 LUMA

Leukocytes of Breast cancer patients (n = 384) Vs matched control (n = 384)

Loss of 5mC

Associated with occurrence of cancer regardless of hormone receptor status [94]

5mC

LINE-1 Pyrosequencing

Colorectal cancer with liver metastases (n = 42) Vs matched primary (n = 24)

No change

No correlation [95]

5mC

LC-MS/MS

Laryngeal cancer (n = 72) Vs adjacent normal laryngeal tissue (n = 72)

Loss of 5mC in both groups

No correlation [96]

5mC

IHC

Prostate Cancer (n = 48) Vs adjacent benign (n = 48)

Loss of 5mC

No correlation with prognostic /pathologic grade [97]

5hmC

IHC

Parathyroid carcinoma (n = 17) Vs Parathyroid adenoma (n = 43)

Loss of 5hmC

Diagnostic criterion for rare disease [98]

5hmC

LC-MS/MS

Bone marrow & Blood from AML (n = 206) Vs Healthy control

Wide range of 5hmC

High 5hmC levels associated with poor prognosis, low levels have no correlation [99]

5hmC

IHC

Glioblastoma (n = 162) Vs healthy control (n = 66)

Loss of 5hmC

Marker for tumor infiltration zones [100]

5caC

IHC

Breast cancer (n = 59) Vs healthy control (n = 28)

Gain of 5caC

No correlation arrived at [38]

5mC, 5hmC, 5fC & 5caC

LC-ESI-MS

Colorectal carcinoma (n = 24) Vs matched tumor-adjacent normal

Loss of 5hmC, 5fC and 5caC. No change in 5mC

No correlation arrived at [39]