Gene promoter methylation in colorectal cancer and healthy adjacent mucosa specimens

Simultaneous Analysis of SEPT9 Promoter Methylation Status, Micronuclei Frequency, and Folate-Related Gene Polymorphisms: The Potential for a Novel Blood-Based Colorectal Cancer Biomarker

“…Deficiencies in the TS enzyme increase the rate of misincorporation of uridylate into DNA, causing DNA strand breaks and other chromosomal damage, thus increasing the predisposition to cancer. Notably, this is in agreement with our finding and other studies reported in the literature on CRC [ 35 , 36 , 37 ], however the limited sample size does not allow for making any definitive conclusions, therefore this should be considered as an explorative study and the finding deserves further investigation.…”

Gene-Specific Methylation Analysis in Thymomas of Patients with Myasthenia Gravis

“…For the MS-HRM analysis we developed protocols according to the literature [37,38]. All analyses were run according to the following conditions: one cycle of 95 °C for 12 min, 60 cycles of 95 °C for 30 s, T a for 30 s and 72 °C for 15 s; followed by an HRM step of 95 °C for 10 s and 50 °C for 1 min, 65 °C for 15 s, and continuous acquisition to 95 °C at one acquisition per 0.2 °C.…”

Plasma Homocysteine and Polymorphisms of Genes Involved in Folate Metabolism Correlate with DNMT1 Gene Methylation Levels

“…This enhanced expression minimizes uracil misincorporation into the DNA and increases the availability of DNA precursors, such that this polymorphism is often associated with cellular growth and risk of human malignancies, including leukemias, lymphomas, breast cancer, and thoracic neoplasms, among others [40][41][42][43]. Less is known about the contribution of TYMS polymorphisms to the DNA methylation levels, even if the TYMS 28-bp tandem repeat polymorphism was associated with gene-specific methylation levels in the blood DNA of patients systemic lupus erythematosus [44], and other TYMS polymorphisms were linked to either global or gene-specific methylation levels in both healthy and cancerous tissues, reinforcing the evidence that DNA synthesis and methylation are interconnected pathways [17,[45][46][47]. The present findings of a correlation between the TYMS 28-bp tandem repeat polymorphism and DNMT1 promoter methylation levels in blood cells highlight the contribution of this gene to DNA methylation, and suggest that further investigation is warranted in human disorders associated to this variant.…”

“…For example, the MTR 2756A > G polymorphism was linked to increased global DNA methylation levels in human leukocytes [30], and carriers of the variant G allele had a significant increase of LINE-1 (long interspersed nuclear element 1) methylation in histologically normal breast tissues, compared to those carrying the common AA genotype [18]. Other studies reported association of this polymorphism with global methylation levels of leukocyte DNA [31], with MTHFR methylation levels in blood DNA of valproate-treated patients with epilepsy [32], and with hypermethylation of tumor suppressor genes in cancer specimens [33] or adjacent healthy tissues [17]. The present finding of a correlation between the MTR 2756A > G polymorphism and DNMT1 promoter methylation levels in blood DNA not only strengthens the contribution of this genetic variant to the DNA methylation levels in leukocytes, but it could also be of relevance for those disorders, such as hematological malignancies, autoimmune/inflammatory disorders, and solid tumors, that are linked to impaired DNMT1 methylation and/or expression [5][6][7][8][9][10][11][12].…”

“…We collected blood samples from 215 healthy individuals, investigated DNMT1 methylation levels in the extracted DNA, and searched for correlation between DNMT1 promoter methylation levels and circulating folate, Hcy, or vitamin B12 levels. In addition, the major polymorphisms on folate-pathway genes, such as methylenetetrahydrofolate reductase (MTHFR) 677C > T (rs1801133) and 1298A > C (rs1801131), methionine synthase (MTR) 2756A > G (rs1805087), methionine synthase reductase (MTRR) 66A > G (rs1801394), thymidilate synthase (TYMS) 28-bp tandem repeat (rs34743033) and 1494 insertion/deletion (indel) (rs34489327), and reduced folate carrier (SLC19A1 or RFC1) 80A > G (rs1051266), as well as both DNMT3A -448A > G (rs1550117) and DNMT3B -149C > T (rs2424913) polymorphisms, are often linked to changes in DNA methylation levels [15][16][17][18][19]. Therefore, we also investigated the contribution of these major polymorphisms of genes involved in the folate pathway to DNMT1 promoter methylation levels.…”