Global DNA demethylation as an epigenetic marker of human brain metastases

被引:17
作者
Barciszewska, Anna-Maria [1 ,2 ]
机构
[1] Poznan Univ Med Sci, Intraoperat Imaging Unit, Chair & Clin Neurosurg & Neurotraumatol, Przybyszewskiego 49, PL-60355 Poznan, Poland
[2] Heliodor Swiecicki Clin Hosp, Dept Neurosurg & Neurotraumatol, Przybyszewskiego 49, PL-60355 Poznan, Poland
关键词
BREAST-CANCER; LUNG-CANCER; OXIDATIVE STRESS; HUMAN-DISEASES; METHYLATION; CARCINOMA; HYPOMETHYLATION; EPIDEMIOLOGY; PATHOGENESIS; MANAGEMENT;
D O I
10.1042/BSR20180731
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 withmolecular 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.
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页数:13
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共 66 条
[1]   The molecular significance of methylated BRCA1 promoter in white blood cells of cancer-free females [J].
Al-Moghrabi, Nisreen ;
Nofel, Asmaa ;
Al-Yousef, Nujoud ;
Madkhali, Safia ;
Bin Amer, Suad M. ;
Alaiya, Ayodele ;
Shinwari, Zakia ;
Al-Tweigeri, Taher ;
Karakas, Bedri ;
Tulbah, Asma ;
Aboussekhra, Abdelilah .
BMC CANCER, 2014, 14
[2]   A high-throughput and sensitive method to measure Global DNA Methylation: Application in Lung Cancer [J].
Anisowicz A. ;
Huang H. ;
Braunschweiger K.I. ;
Liu Z. ;
Giese H. ;
Wang H. ;
Mamaev S. ;
Olejnik J. ;
Massion P.P. ;
Del Mastro R.G. .
BMC Cancer, 8 (1)
[3]   Updates in the management of brain metastases [J].
Arvold, Nils D. ;
Lee, Eudocia Q. ;
Mehta, Minesh P. ;
Margolin, Kim ;
Alexander, Brian M. ;
Lin, Nancy U. ;
Anders, Carey K. ;
Soffietti, Riccardo ;
Camidge, D. Ross ;
Vogelbaum, Michael A. ;
Dunn, Ian F. ;
Wen, Patrick Y. .
NEURO-ONCOLOGY, 2016, 18 (08) :1043-1065
[4]   The Degree of Global DNA Hypomethylation in Peripheral Blood Correlates with That in Matched Tumor Tissues in Several Neoplasia [J].
Barciszewska, Anna-Maria ;
Nowak, Stanislaw ;
Naskret-Barciszewska, Miroslawa Z. .
PLOS ONE, 2014, 9 (03)
[5]   The increasing roles of epigenetics in breast cancer: Implications for pathogenicity, biomarkers, prevention and treatment [J].
Basse, Clemence ;
Arock, Michel .
INTERNATIONAL JOURNAL OF CANCER, 2015, 137 (12) :2785-2794
[6]   DNA methylation dynamics in health and disease [J].
Bergman, Yehudit ;
Cedar, Howard .
NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2013, 20 (03) :274-281
[7]   DNA Methylation and Demethylation in Mammals [J].
Chen, Zhao-xia ;
Riggs, Arthur D. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (21) :18347-18353
[8]   The pivotal role of pathology in the management of lung cancer [J].
Davidson, Morgan R. ;
Gazdar, Adi F. ;
Clarke, Belinda E. .
JOURNAL OF THORACIC DISEASE, 2013, 5 :S463-S478
[9]   Histopathological transformation to small-cell lung carcinoma in non-small cell lung carcinoma tumors [J].
Dorantes-Heredia, Rita ;
Manuel Ruiz-Morales, Jose ;
Cano-Garcia, Fernando .
TRANSLATIONAL LUNG CANCER RESEARCH, 2016, 5 (04) :401-412
[10]   Brain metastasis in lung cancer: Building a molecular and systems-level understanding to improve outcomes [J].
Ebben, Johnathan D. ;
You, Ming .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2016, 78 :288-296