Global DNA demethylation as an epigenetic marker of human brain metastases.
Anna-Maria BarciszewskaPublished in: Bioscience reports (2018)
Brain metastases are the most common intracranial tumors in adults. They usually originate from: lung, breast, renal cell and gastrointestinal cancers, as well as melanoma. Prognosis for brain metastases is still poor and classical treatment combining surgery and radiation therapy should be strongly supported with molecular approaches. However, their successful application depends on a deep understanding of not only genetic, but also epigenetic background of the disease. That will result in an earlier and more precise diagnosis, successful treatment, as well as individualized estimation of clinical outcomes and prognosis. It has already been shown that the epigenetic machinery plays a crucial role in cancer biology, development, and progression. Therefore, we decided to look for metastasis through changes in the most studied epigenetic mark, 5-methylcytosine (m5C) in DNA. We performed global analysis of the m5C contents in DNA isolated from the brain metastatic tumor tissue and peripheral blood samples of the same patients, using thin layer chromatography separation of radioactively labeled nucleotides. We found that the m5C level in DNA from brain metastases: changes in the broad range, overlaps with that of blood, and negatively correlates with the increasing tumor grade. Because the amount of m5C in tumor tissue and blood is almost identical, the genomic DNA methylation can be a useful marker for brain metastases detection and differentiation. Our research creates a scope for future studies on epigenetic mechanisms in neuro-oncology and can lead to development of new diagnostic methods in clinical practice.
Keyphrases
- brain metastases
- dna methylation
- small cell lung cancer
- circulating tumor
- genome wide
- gene expression
- single molecule
- cell free
- radiation therapy
- peripheral blood
- copy number
- clinical practice
- end stage renal disease
- newly diagnosed
- squamous cell carcinoma
- nucleic acid
- minimally invasive
- ejection fraction
- mass spectrometry
- endothelial cells
- palliative care
- liquid chromatography
- chronic kidney disease
- cell therapy
- peritoneal dialysis
- stem cells
- coronary artery bypass
- prognostic factors
- young adults
- quantum dots
- combination therapy
- sensitive detection
- functional connectivity