selective advantage upon a stem cell. However, reduced or absent expression of MGMT would cause increased rates of mutation, and one or more of the mutated genes may provide the cell with a selective advantage. The expression-deficient MGMT gene could then be carried along as a selectively neutral or only slightly deleterious passenger (hitch-hiker) gene when the mutated stem cell generates an expanded clone. The continued presence of a clone with an epigenetically repressed MGMT would continue to generate further mutations, some of which could produce a tumor. Deficiency with exogenous damage MGMT deficiency alone may not be sufficient to cause progression to cancer. Mice with a homozygous mutation in MGMT did not develop more cancers than wild-type mice when grown without stress. However, stressful treatment of mice with azoxymethane and dextran sulphate caused more than four colonic tumors per MGMT mutant mouse, but less than one tumor per wild-type mouse. Repression in coordination with other DNA repair genes In a cancer, multiple DNA repair genes are often found to be simultaneously repressed. In one example, involving MGMT, Jiang et al. 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. Among the 27 DNA repair genes evaluated, 13 DNA repair genes, MGMT, NTHL1, OGG1, SMUG1, ERCC1, ERCC2, ERCC3, ERCC4, MLH1, MLH3, RAD50, XRCC4 and XRCC5 were all significantly down-regulated in all three grades (II, III and IV) of astrocytomas. The repression of these 13 genes in lower grade as well as in higher grade astrocytomas suggested that they may be important in early as well as in later stages of astrocytoma. In another example, Kitajima et al. found that immunoreactivity for MGMT and MLH1 expression was closely correlated in 135 specimens of gastric cancer and loss of MGMT and hMLH1 appeared to be synchronously accelerated during tumor progression. Deficient expression of multiple DNA repair genes are often found in cancers, and may contribute to the thousands of mutations usually found in cancers (see mutation frequencies in cancers). Interactions O6-methylguanine-DNA methyltransferase has been shown to interact with estrogen receptor alpha. See also Ada Ogt 6-O-Methylguanine DNA methyltransferase Methyltransferase References Further reading DNA repair