BRCA1 Promoter Methylation in Ovarian Cancer

DNA methylation is a process by which methyl groups are added to DNA. Methylation modifies the function of the DNA, typically acting to suppress gene transcription. DNA methylation is essential for normal development and is associated with a number of key processes including genomic imprinting, X-chromosome inactivation, suppression of repetitive elements, and carcinogenesis.

Two of DNA’s four nucleotides, cytosine, and adenine, can be methylated. Adenine methylation is restricted to prokaryotes. The rate of cytosine DNA methylation differs strongly between species: 14% of cytosines are methylated in Arabidopsis thaliana, 4% in Mus musculus, 2.3% in Escherichia coli, 0.03% in Drosophila, and virtually none (< 0.0002%) in yeast species.

DNA methylation can stably alter the expression of genes in cells as cells divide and differentiate from embryonic stem cells into specific tissues. The resulting change is normally permanent and unidirectional, preventing a cell from reverting to a stem cell or converting into a different cell type.

However, DNA methylation can be removed either passively, by dilution as cells divide, or by a faster, active, process. The latter process occurs via hydroxylation of the methyl groups that are to be removed, rather than by complete removal of methyl groups. DNA methylation is typically removed during zygote formation and re-established through successive cell divisions during development. Methylation modifications that regulate gene expression are usually heritable through mitotic cell division; some methylation is also heritable through the specialized meiotic cell division that creates egg and sperm cells, resulting in genomic imprinting. DNA methylation suppresses the expression of endogenous retroviral genes and other harmful stretches of DNA that have been incorporated into the host genome over time. DNA methylation also forms the basis of chromatin structure, which enables a single cell to grow into multiple organs or perform multiple functions. DNA methylation also plays a crucial role in the development of nearly all types of cancer.

DNA methylation is an important regulator of gene transcription and a large body of evidence has demonstrated that genes with high levels of 5-methylcytosine in their promoter region are transcriptionally silent and that DNA methylation gradually accumulates upon long-term gene silencing. DNA methylation is essential during embryonic development, and in somatic cells, patterns of DNA methylation are generally transmitted to daughter cells with a high fidelity. Aberrant DNA methylation patterns – hypermethylation and hypomethylation compared to normal tissue – have been associated with a large number of human malignancies. Hypermethylation typically occurs at CpG islands in the promoter region and is associated with gene inactivation. A lower level of leukocyte DNA methylation is associated with many types of cancer. Global hypomethylation has also been implicated in the development and progression of cancer through different mechanisms. Typically, there is hypermethylation of tumor suppressor genes and hypomethylation of oncogenes.

Methylation defects are tied to a wide variety of conditions:

Cancer

Autism

Down’s Syndrome

Diabetes

Fibromyalgia

Chronic Fatigue SyndromeDNA Methylation

Pulmonary Embolism

Addictive Behavior

Allergies or Multiple Chemical Sensitivities

Atherosclerosis

Spina Bifida

Cleft Palate or Neural Tube Defects

Multiple Sclerosis and other Autoimmune Disorders

Insomnia

Miscarriages

Bipolar or manic depression

Hypothyroidism

Dementia

Alzheimer’s

Schizophrenia

Anxiety

Neuropathy

Lyme Disease

Chronic Viral Infections



 

 

BRCA1-Methylation-Status-in-Ovarian-Cancer

 

 

 

 

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