Global DNA demethylation as an epigenetic marker of human brain metastases

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 (m(5)C) in DNA. We performed global analysis of the m(5)C 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 m(5)C 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 m(5)C 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.