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Table 1 Literature identified hypermethylated loci in head and neck squamous cell carcinomas, according to frequency, methodology and univariate correlation with survival a

From: Quantitative methodology is critical for assessing DNA methylation and impacts on correlation with patient outcome

Gene % Methylation (n) Publication Methodologyb Correlation with outcomec
ABO 33 (30) [28] MSP, MCA -
APC 9-71%    
13 (47) [29] MSP -
17 (79) [30] MS-MLPA N
71 (84)d [31] MSP -
15 (34) [22] MSP, MCA -
18 (77) [27] Nested MSP N
9 (126)e [32] MS-MLPA -
ATM 0-88%    
42 (24)f [33] MSP -
88 (84)d [31] MSP -
0 (37) [34] Pyrosequencing -
25 (100) [18] MSP W
1 (126 )e [32] MS-MLPA -
BRCA1 0-95%    
95 (58)d [20] Pyrosequencing -
0 (89) [35] MSP -
0 (126)e [32] MS-MLPA -
CDH1 0-88%    
0 (32) [36] MSP -
18 (48) [37] qMSP N
88 (43) [38] MSP -
33 (340)f [39] MSP I
13 (38) [40] MSP I
43 (54) [41] MSP -
62 (76) [42] MSP -
64 (86) [25] RE-MSP Wg
78 (23) [43] MSP -
43 (190) [9] MSP N
42 (47) [29] MSP -
43 (77) [27] Nested MSP W
38 (37) [34] Pyrosequencing -
42 (79) [44] Pyrosequencing -
36 (80) [45] MSP -
66 (33)h [46] qMSP N
35 (99) [47] RE-MSP -
35 (55)f [48] MSP -
CDH13 10-34%    
34 (79) [30] MS-MLPA N
10 (126)e [32] MS-MLPA -
CDKN2A (P16) 0-95%    
38 (56) [49] MSP -
49 (73) [50] MSP N
36 (47) [51] MSP N
49 (51) [52] MSP -
12 (61) [53] MSP N
48 (92) [54] qMSP -
22 (48) [37] qMSP N
78 (40)h [55] MSP N
13 (79) [30] MS-MLPA N
63 (43) [38] MSP -
5 (42) [40] MSP N
60 (54) [41] MSP -
87 (38) [7] MSP -
17 (24)f [56] MSP -
27 (56 )h [57] RE-MSP -
79 (75) [58] MSP I
20 (20) [59] MSP -
44 (126) [9] MSP N
59 (47) [29] MSP -
58 (77) [27] Nested MSP N
95 (41) [60] MSP -
26 (37) [34] Pyrosequencing -
28 (79) [44] Pyrosequencing -
24 (45)f [61] MSP -
20 (20) [62] RE-MSP -
33 (80) [45] MSP -
29 (96) [63] MSPi N
47 (30) [10] MSP -
29 (116) [64] MSP W
27 (95) [65] MSP -
20 (121) [66] MSP -
29 (52)h [46] qMSP W
23 (99) [47] RE-MSP N
8 (51)f [48] MSP -
23 (30) [67] RE-MSP -
0 (126)e [32] MS-MLPA -
DAPK1 7-81%    
14 (79) [30] MS-MLPA N
81 (43) [38] MSP -
11 (44) [40] MSP N
60 (54) [41] MSP -
76 (41) [68] MSP -
42 (290) [9] MSP N
37 (77) [27] Nested MSP N
30 (47) [29] MSP -
19 (32) [36] MSP -
45 (20) [59] MSP -
39 (18) [60] MSP -
24 (80) [45] MSP -
7 (96) [63] MSPi N
33 (30) [10] MSP -
18 (95) [65] MSP -
42 (33)h [46] qMSP N
20 (49)f [48] MSP -
12 (126)e [32] MS-MLPA -
ERCC1 51 (84) [19] MSP N
MGMT 18-74%    
30 (47) [51] MSP N
53 (51) [52] MSP -
10 (20) [53] Pyrosequencing Wj
30 (88) [53] MSP Wj
36 (44)h [69] MSP -
31 (32) [36] MSP -
43 (40) [40] MSP N
53 (54) [41] MSP -
74 (76) [42] MSP -
50 (20) [59] MSP -
27 (212) [9] MSP N
54 (41) [68] MSP -
31 (37) [34] Pyrosequencing -
28 (21) [70] MSP -
23 (30) [10] MSP -
33 (95) [65] MSP -
21 (33)h [46] qMSP N
38 (47) [29] MSP -
34 (77) [27] Nested MSP N
41 (99) [47] RE-MSP -
25 (52)f [48] MSP -
18 (94) [71] MSP W
MLH1 0-88%    
26 (47) [29] MSP -
18 (28) [72] MSP -
0 (20) [73] RE-MSP -
23 (62) [49] MSP -
23 (47) [51] MSP N
47 (116)e [74] RE-MSP -
37 (123) [75] RE-MSP -
88 (8) [76] MSP -
69 (54) [41] MSP -
0 (37) [34] Pyrosequencing -
29 (49) [17] MSP -
76 (50) [77] MSP -
0 (96) [63] MSPi N
8 (99) [47] RE-MSP -
14 (43)f [48] MSP -
0 (126)e [32] MS-MLPA -
RASSF1A 0-44%    
17 (24) [78] RE-MSP -
12 (66) [53] MSP N
2 (41) [40] MSP N
18 (54) [41] MSP -
0 (32) [36] MSP -
32 (41) [68] MSP -
38 (47) [27] MSP -
44 (18) [60] MSP -
22 (482)h [8] dHPLC N
8 (80) [45] MSP -
33 (33)h [46] qMSP N
6 (50)f [48] MSP -
11 (126)e [32] MS-MLPA -
RUNX3 18-70%    
70 (30) [79] MSP -
26 (47) [29] MSP -
25 (76) [21] MSP N
18 (45)f [61] MSP -
  1. aMethylation frequency is only reported for intra-tumoral methylation. A summary of the range of reported methylation is presented in bold font when available.
  2. bMethodology: dHPLC, denaturing high-performance liquid chromatography; MCA, melting curve analysis; MSP, methylation-specific PCR; MS-MLPA, methylation specific multiplex ligation-dependent probe amplification; RE-MSP, restriction enzyme MSP. A prefixed ‘q’ indicates the use of a quantitative version of the methodology.
  3. cCorrelation with outcome: W, Worse; I, Improved; N, None; - Not performed.
  4. dthese studies identified similar frequencies or quantities of methylation as control samples.
  5. ethese studies included samples with mixed histotypes, not just squamous cell carcinomas.
  6. fthese studies tested for the presence of the Human Papillomavirus.
  7. gthis study determined correlation with outcome based on immunohistochemistry.
  8. hthese studies include patients with betel nut or areca nut exposure.
  9. ithese studies quantified the band intensity on gel electrophoresis.
  10. jthis study examined a subset of samples that had demonstrated methylation with MSP, with quantitative methodology.