Although alkylating mutagens preferentially modify the guanine base at the N7 position, O6-alkyl-guanine is a major carcinogenic lesion in DNA.

In patients with glioblastoma, a severe type of brain tumor, the cancer medicine temozolomide is more effective in those with a methylation of the gene's promoter.

[10] For testing of the MGMT promoter methylation status in the clinical setting, DNA-based methods such as methylation-specific polymerase chain reaction (MS-PCR) or pyrosequencing are preferred over immunohistochemical or RNA- based assays.

[11] In patients with pituitary tumours, MGMT can predict the clinical and radiological response to treatment with temozolomide.

In 1985 Yarosh summarized the early work that established m6G as the alkylated base in DNA that was the most mutagenic and carcinogenic.

The loss of MGMT function leads to a higher rate of mutations, promoting the formation and progression of tumors.

Hence, MGMT can be used as a prognostic marker to predict the likelihood of treatment response and to guide the selection of appropriate therapies.

As pointed out by Rubin, "The vast majority of studies in cancer research has been done on well-defined tumors in vivo, or on discrete neoplastic foci in vitro.

"[48] Similarly, Vogelstein et al.[49] point out that more than half of somatic mutations identified in tumors occurred in a pre-neoplastic phase (in a field defect), during growth of apparently normal cells.

In the Table above, MGMT deficiencies were noted in the field defects (histologically normal tissues) surrounding most of the cancers.

[52] In one example, involving MGMT, Jiang et al.[53] conducted a study where they evaluated the mRNA expression of 27 DNA repair genes in 40 astrocytomas compared to normal brain tissues from non-astrocytoma individuals.