Table 1. List of methylated/silenced tumor suppressor genes (TSGs) involved in cell signaling in nasopharyngeal carcinoma (NPC).

Classification	TSG	Full name	Other names	Location	Functions	Alterations in NPC	Refs
Ras GTPase signaling	DAB2	Disabled homolog 2, mitogen-responsive phosphoprotein (Drosophila)	DOC2	5p13	Mitogen responsive phosphoprotein, suppresses the mitogenic signaling via Ras pathway, cell differentiation, cell proliferation	Methylated	[15]
	RASAL1	RAS protein activator like 1 (GAP1 like)	RASAL	12q23-q24	Ras GTPase-activating protein, negatively regulates Ras signaling	Methylated	[9]
	RASSF1	Ras association (RalGDS/AF-6) domain family 1	RASSF1A	3p21.3	RAS effector protein, Ras signaling, cell cycle arrest, apoptosis, DNA repair, inhibits the accumulation of cyclin D1	Methylated, mutated	[10]–[14]
	SCGB3A1	Secretoglobin, family 3A, member 1	HIN1	5q35-qter	AKT signaling pathway, cell communication	Methylated	[16]
Rho GTPase signaling	DLC1	Deleted in liver cancer 1	ARHGAP7, STARD12, p122-RhoGAP	8p22.3	Cell cytoskeleton organization, GTPase activator, signal transduction, cell adhesion, invasion	Methylated, deleted (LOH)	[18]
p53 signaling	UCHL1	Ubiquitin carboxyl-terminal esterase L1 (Ubiquitin thiolesterase)	PARK5, PGP9.5	4p14	Apoptosis, binds p53/MDM2 complex and activates p53 signaling	Methylated	[23]
	TP73	Tumor protein p73	p73	1p36.3	Cell cycle, DNA damage response, apoptosis, transcription factor	Methylated	[10]
Wnt/β-catenin signaling	WIF1	WNT inhibitory factor 1	WIF-1	12q14.3	Wnt-signaling pathway, binds and inhibits	Methylated	[26]
					WNT proteins, protein-tyrosine kinase activity
Cell cycle signaling	BRD7	Bromodomain containing 7		16q12	Transcriptional regulation, cell cycle regulation	Methylated	[31]
	CDKN2A	Cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)	p16, INK4A, MTS1, CDK4I, CDKN2, p16INK4A	9p21	Cell cycle regulation p16: inhibits CDK4 kinase	p16: mutated, methylated, deleted	[10],[12],[13],[30]
	ARF	Alternate open reading frame	p14, p14ARF		ARF: stabilizes p53, interacts with MDM2	ARF: methylated, deleted
	CDKN2B	Cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4)	p15, MTS2, TP15, INK4B	9p21	Cyclin-dependent kinase inhibitor for CDK4 and CDK6, cell cycle regulation	Methylated	[10],[12],[13]
	CHFR	Checkpoint with forkhead and ring finger domains	RNF116, RNF196	12q24.33	Mitotic checkpoint protein early in G2-M transition, cell cycle regulation	Methylated	[35]
	FHIT	Fragile histidine triad gene	FRA3B, AP3Aase	3p14.2	Cell cycle regulation, G1-S phase checkpoint, DNA-damage response, nucleotide and nucleic acid metabolism	Deleted, abnormal transcripts, methylated	[37]
	MIP0L1	Mirror-image polydactyly 1		14q13.3	Cell cycle (G1-S phase) regulation, up-regulates p21 and p27 protein	Methylated, deleted (LOH)	[32]
	PTPRG	Protein tyrosine phosphatase, receptor type, G	PTPG, HPTPG, RPTPG	3p21-p14	Cell proliferation, cell cycle regulation, signal transduction	Methylated, deleted (LOH)	[38]
DNA damage signaling	GADD45G	Growth arrest and DNA-damage-inducible, gamma	GADD45gamma, CR6, GRP17	9q22.1-q22.2	DNA-damage response	Methylated, no mutation	[34]
	MGMT	0-6-methylguanine-DNA methyltransferase		10q26	DNA repair, senses and integrates DNA damage/repair-related signals with replication, cell cycle and genomic stability	Methylated	[10],[14]
	MLH1	Mut L homolog 1, colon cancer, nonpolyposis type 2 (E. coli)	hMLM, HNPCC, FCC2	3p21.3	DNA mismatch repair protein, cell cycle G2/M arrest	Methylated	[10],[13]
Cell adhesion signaling	CDH1	Cadherin 1, type 1, E-cadherin (epithelial)	CDHE, ECAD, LCAM, CD324	16q22.1	Classical cadherin, calcium dependent cell-cell adhesion, proliferation, invasion, metastasis	Methylated	[10],[13],[39]
	CADM1	Cell adhesion molecule 1	IGSF4, TSLC1, NECL2, RA175, synCAM1, SglGSF	11q23.2	Ca2+/Mg2+-independent cell-cell adhesion, apoptosis	Methylated	[42]
	MMP19	Matrix metallopeptidase 19	MMP18, RASI-1	12q14	Matrix metalloproteinase, anti-angiogenesis	Methylated, deleted (LOH)	[45]
	OPCML	Opioid binding protein/cell adhesion molecule-like	OPCM, OBCAM	11q25	IgLON immunoglobulin protein, cell adhension	Methylated	[46]
	PCDH10	Protocadherin 10	OL-PCDH,PCDH19	4q28.3	Protocadherin, cell-cell adhesion, apoptosis, cell signaling	Methylated	[43]
	TFPI2	Tissue factor pathway inhibitor 2	PP5	7q22	Serine protease inhibitor, metastasis	Methylated	[47]
	THBS1	Thrombospondin 1	TSP, THBS, TSP1	15q15	Adhesive glycoprotein, cell-to-cell and cell-to-matrix interactions, angiogenesis, cell signaling, cell motility	Methylated	[10]
Apoptosis signaling	CASP8	Caspase 8, apoptosis-related cysteine peptidase	CAP4, MACH, MCH5, FLICE	2q33-q34	Apoptosis	Methylated	[10]
	DAPK1	Death-associated protein kinase 1	DAPK	9q34.1	Positive mediator of gamma-interferon induced apoptosis	Methylated	[12]–[14]
	GSTP1	Glutathione S-transferase pi 1	DFN7, GST3	11q13	Apoptosis, metabolism, energy pathways	Infrequently methylated	[14]