Mutational changes in the promoter regions of MTHFR genes from patients with
hyperhomocysteinemia and PTEN genes from patients with endometrial and ovarian
tumors were studied. An increased level of
homocysteine was found in a part of the patients with a heterozygous C677T mutation in the MTHFR gene, although a moderate
hyperhomocysteinemia is usually associated with homozygous mutation. We hypothesized that, in this case, the allele lacking the C677T mutation may be inactivated by the promoter mutation. The sequencing of both
DNA strands of the minimal promoter region of the MTHFR gene in ten patients did not reveal any mutation, which implied another mechanism of the development of
hyperhomocysteinemia in these patients. A PCR analysis of the minimal promoter region of the
tumor suppressor PTEN in the presence of
2-pyrrolidone in 101 patients from Moscow clinics revealed changes in it in patients with endometrial (56%) or ovarian (29%)
cancer, as well as in patients with
endometrial hyperplasia and benign ovarian
tumors (34.6 and 29%, respectively). It was presumed that the found PTEN gene promoters may arise from epigenetic alterations (erroneous methylation) or may (more rarely) be induced by mutations. As a result of the studies, new molecular markers associated with endometrial and ovarian
tumors were revealed and a simple and effective method of detection of these markers was developed.