Table 1 Summary of methylation markers
Author | Marker | Study population | Response to treatment | Treatment given | Other findings |
|---|---|---|---|---|---|
Kim 2002 [36] | ATM methylation | Human HNPCC-deficient CRC cell lines | Hypermethylation associated with increased response to IR | 10Â Gy radiation | Reversal of gene suppression and increased response after AZA treatment |
Hofstetter 2010 [39] | P16 and hMLH-1 methylation | Human CRC cell lines (×4) | Demethylation of markers resulted in enhanced radiation sensitivity | 10 Gy radiation | N/A |
Giotopoulos 2006 [41] | Quantitative DNA 5-methyl-cytosine content analysis | Murine bone marrow cells | Hypomethylation of bone marrow associated with increased radiation sensitivity | 3Â Gy radiation | N/A |
Ebert 2012 [45] | TFAP2E methylation | 110 human locally advanced rectal cancers | Hypermethylation associated with markedly reduced response to neoadjuvant CRT (10 vs 82Â %) | Treatment dose radiotherapy with combination chemotherapeutic agents | Possible mechanism via WNT signalling pathway |
Jo 2012 [23] | CIMP status +/− | 150 human locally advanced rectal cancers | No association of pathological response to IR with CIMP status | Treatment dose radiotherapy and 5-FU chemotherapy | Increased risk of distant metastases and poorer 5-year survival with CIMP + |
Sun 2014 [47] | MGMT methylation | 219 rectal cancer patients | MGMT hypermethylation associated with increased tumour regression | Treatment dose radiotherapy and 5-FU chemotherapy | N/A |
Molinari 2013 [48] | TIMP3 methylation | 74 rectal cancer patients | TIMP3 hypomethylation associated with poor tumour regression | Treatment dose radiotherapy and 5-FU chemotherapy | Several genes including APC found differentially methylated between tumour and normal mucosa |
Kohonen-Corish 2013 [51] | CIMP H/L and CDKN2A methylation | 381 early rectal cancers | Not examined | Primary surgery for majority of patients | CIMP H or CDKN2A not independently associated with survival. CDKN2A and KRAS mutation associated with poor survival and increased recurrence |
Bae 2013 [54] | CIMP status H/L/0 | 168 rectal cancers (stages I–IV) | Not examined | Primary surgery only | CIMP H associated with poor survival |
Benard 2013 [55] | LINE-1 methylation | 94 early rectal cancers | Not examined | Primary surgery only | Hypomethylation of LINE-1 associated with increased risk of recurrence and poor survival |
Gaedcke 2014 [57] | Whole-genome methylation | 165 locally advanced rectal cancer patients | Not examined | 3 cohorts including neoadjuvant 5-FU, oxaliplatin and radiotherapy | 10 differentially methylated regions (DMRs), hypermethylation of which predicts improved disease-free survival |
De Maat 2010 [58] | MINT loci | 251 rectal cancer patients (stages I–III) | Not examined | Primary surgery only | MINT 3 hyper- and MINT 17 hypomethylation predicts reduced risk of recurrence similar to unselected patients undergoing neoadjuvant treatment |