Global DNA demethylation as an epigenetic marker of human brain metastases

Abstract

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.

Total DNA Methylation Changes Reflect Random Oxidative DNA Damage in Gliomas

“…DNA isolation from blood and tissue samples was performed, as previously described [19,20,21,23]. DNA purity was controlled with UV absorbance measurements at 260 and 280 nm.…”

“…DNA hydrolysis, labeling, and TLC chromatography were performed as previously described [19,20,21,22,23]. The radioactive intensity of spots corresponding to m 5 C, C (cytosine), and T (thymine) was used for calculations.…”

“…Therefore, DNA methylation changes (m 5 C) are regarded as a good measure of cancer development and progression [18]. We have previously shown that the total contents of m 5 C can serve as a marker in the diagnosis of various diseases and aging, as well as for the molecular description of the treatment process [19,20,21,22,23]. Therefore, the implementation of total DNA methylation analysis, rather than more specific methods (like methylation matrices, methylome sequencing), is a useful approach in clinical practice [24,25].…”

<p>Peripheral Blood Leukocyte N6-methyladenosine is a Noninvasive Biomarker for Non-small-cell Lung Carcinoma</p>

“…This random and global process might not be limited to a certain area or cell type, not just in foci where tumors are localized. 31,32 In fact, it has been known that cancer can induce distant changes on myeloid cells function, mobilization, and differentiation, well before clinically evident metastasis develops. 33 In this study, we identified elevated leukocyte m6A were mainly from lymphocytes and monocytes, and they had a strong correlation in the NSCLC group, but not in the NC group.…”

Total DNA methylation as a biomarker of DNA damage and tumor malignancy in intracranial meningiomas

“…That tendency is comparable to our previous results for brain gliomas [33] and Table 3 Data summary of total DNA methylation in tumor tissue and peripheral blood samples of 29 patients with various meningioma types with numerical amount and grade distribution. Median age (in years) in the histological subclasses, and female to male (F:M) ratio is also given metastases [49]. However, the mean total DNA methylation levels (R) in those cases were generally lower compared to meningiomas reflecting the known higher malignancy of gliomas and metastasis.…”