Epigenetic heterogeneity in cancer

Guo, Mingzhou; Peng, Yaojun; Gao, Aiai; Du, Chen; Herman, James G.

doi:10.1186/s40364-019-0174-y

Biomarker Research

Table 1 Aberrant epigenetic changes of the major components in cancer-related signaling pathways

From: Epigenetic heterogeneity in cancer

Signaling pathway	Gene	Major role	Alteration	Tumor type	Ref
Cell cycle regulation	p16 (CDKN2A)	G1-S transition	promoter hypermethylation	oral and oropharyngeal squamous cell carcinoma, HCC, GC, CRC, esophageal, lung and ovarian cancer	[44, 45]
	CHFR	G2-M transition	promoter hypermethylation	NSCLC, GC, CRC, BC,, HCC, nasopharyngeal, bladder, esophageal, cervical and endometrial cancers	[46]
	RASSF1A	M-phase progression	promoter hypermethylation	BC, head and neck cancer, gynecological, lung, prostate, bladder, brain, gastrointestinal, renal and renal cancers, sarcoma melanoma	[47]
	Chk2	checkpoint kinase 2, damage sensors	promoter hypermethylation	Glioma, Hodgkin’s lymphoma, NSCLC	[48,49,50]
	ATM	cell cycle checkpoint kinase	promoter hypermethylation	BC, gastric lymphoma, glioma, colonic cancer, adenoma	[51]
DNA damage repair	BRCA1	HR repair	promoter hypermethylation	NSCLC, CRC, breast, ovarian, bladder and pancreatic cancers	[52,53,54,55]
	BRCA2	HR repair	promoter hypermethylation	NSCLC, BC and ovarian cancers	[56]
	FANCF	FA complementation group F	promoter hypermethylation	head and neck cancers, NSCLC, ovarian, breast and cervical cancer	[57]
	XRCC5	X-ray repair cross complementing 5, component of NHEJ	promoter hypermethylation	NSCLC, glioma	[56, 58]
	WRN	Werner syndrome RecQ like helicase, component of BER	promoter hypermethylation	NSCLC, CRC, GC, prostate, breast and thyroid cancers, non-Hodgkin lymphoma, chondrosarcomas	[59]
	MSH2	MutS family protein, MMR ATPase	promoter hypermethylation	hereditary nonpolyposis colorectal cancer, HCC	[60, 61]
	RAD23B (hHR23B)	RAD23 homolog B, NER protein	promoter hypermethylation	myeloma	[62]
Wnt pathway	WNT5A	ligand	promoter hypermethylation, histone modification	CRC	[63]
	WNT2	ligand	histone modification	CRC	[64]
	WIF1	sequesters Wnt proteins	promoter hypermethylation	HCC, GC, BC, CRC, lung cancer	[65,66,67,68]
	DKK	LRP5/6 antagonist	promoter hypermethylation, histone modification	NSCLC, BC, CRC, GC, HCC	[63, 69,70,71]
	Cadherin	CTNNB1 translocation	promoter hypermethylation	BC, NSCLC, CRC, GC, HCC, ESSC, CLL, pancreatic, bladder and prostate cancers	[72]
	APC	binds CTNNB1 to destruction complex	promoter hypermethylation, histone modification	GC, CRC, ESCC, BC, NSCLC, HCC and prostate cancer	[73]
	GSK3β	phosphorylates CTNNB1	promoter hypermethylation	CRC	[74]
TGF-β pathway	RUNX3	interacts with SMADs	promoter hypermethylation	GC, HCC, CRC, BC, lung, bladder and pancreatic cancers	[75]
	SMAD6/7	inhibits TGF-β-induced SMAD3 activation	promoter hypermethylation, histone methylation	Lung cancer	[76]
	DACH1	interacts with NCoR and SMAD4	promoter hypermethylation	GC, ESSC, CRC, HCC, endometrial, lung and renal cancers	[42, 77,78,79]
	FBXO32	target of TGF-β signaling pathway	promoter hypermethylation	ESSC, GC and ovarian cancer	[80, 81]
NF-κB pathway	p65 (RelA)	major functional subunit of NF-κB	histone modification	CRC, osteosarcoma	[82, 83]
	ZNF382	inhibitor of NF-κB	promoter hypermethylation	GC, ESCC, CRC, BC and nasopharyngeal cancer	[84]
	ZNF545	inhibitor of NF-κB	promoter hypermethylation	HCC	[43]
	CXCL14	inhibitor of NF-κB	promoter hypermethylation	CRC	[85]
Akt pathway	ADAMTS9	inhibitor of Akt signaling	promoter hypermethylation	CRC	[86]
	RAI2	inhibitor of Akt signaling	promoter hypermethylation	CRC	[87]
	HIN-1	inhibitor of Akt signaling	promoter hypermethylation	NSCLC	[88]
p53 pathway	RASSF10	agonist of p53 signaling	promoter hypermethylation	CRC, HCC, papillary thyroid carcinoma	[89, 90]
	BCL6B	agonist of p53 signaling	promoter hypermethylation	HCC, CRC, GC	[91, 92]
	DLEC1	target of p53 signaling	promoter hypermethylation	ESCC, nasopharyngeal, lung carcinomas	[93]
Retinoid acid pathway	CRBP1	retinol-binding protein	promoter hypermethylation	CRC, ESSC, gastrointestinal carcinoma, lymphoma, prostate cancer	[94,95,96,97,98]
Retinoid acid pathway	RARbeta2	retinoic acid receptor	promoter hypermethylation	BC, lymphoma, gastrointestinal carcinomas, bladder cancer	[97, 99, 100]
Hedgehog pathway	PTCH1	primary receptor	promoter hypermethylation, histone modification	GC, BC, medulloblastoma, basal cell carcinomas	[101,102,103]
	SHH	ligand	promoter hypomethylation, histone modification	GC, BC	[104, 105]
	HHIP	ligand sequestering	promoter hypermethylation	LAC, GC, HCC, medulloblastoma, pancreatic cancer	[106]
	GLI1	transcription activator	histone modification	BC	[107]
	GLI3	transcription repressor	promoter hypomethylation	GC	[108]

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ISSN: 2050-7771

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