Differential and Common Signatures of miRNA Expression and Methylation in Childhood Central Nervous System Malignancies: An Experimental and Computational Approach

George I Lambrou; Myrto Poulou; Krinio Giannikou; Marios Themistocleous; Apostolos Zaravinos; Maria Braoudaki

doi:10.3390/cancers13215491

Differential and Common Signatures of miRNA Expression and Methylation in Childhood Central Nervous System Malignancies: An Experimental and Computational Approach

Cancers (Basel). 2021 Oct 31;13(21):5491. doi: 10.3390/cancers13215491.

Authors

George I Lambrou¹, Myrto Poulou², Krinio Giannikou³, Marios Themistocleous⁴, Apostolos Zaravinos^{5

6}, Maria Braoudaki⁷

Affiliations

¹ Choremeio Research Laboratory, First Department of Pediatrics, National and Kapodistrian University of Athens, 11527 Athens, Greece.
² Department of Medical Genetics, Medical School, National and Kapodistrian University of Athens, 15772 Athens, Greece.
³ Cancer Genetics Laboratory, Division of Pulmonary and Critical Care Medicine and of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
⁴ Department of Neurosurgery, "Aghia Sofia" Children's Hospital, 11527 Athens, Greece.
⁵ Department of Life Sciences, School of Sciences, European University Cyprus, Nicosia 2404, Cyprus.
⁶ Basic and Translational Cancer Research Center (BTCRC), Cancer Genetics, Genomics and Systems Biology Group, European University Cyprus, Nicosia 1516, Cyprus.
⁷ Department of Life and Environmental Sciences, School of Life and Health Sciences, University of Hertfordshire, Hertfordshire AL10 9AB, UK.

Abstract

Epigenetic modifications are considered of utmost significance for tumor ontogenesis and progression. Especially, it has been found that miRNA expression, as well as DNA methylation plays a significant role in central nervous system tumors during childhood. A total of 49 resected brain tumors from children were used for further analysis. DNA methylation was identified with methylation-specific MLPA and, in particular, for the tumor suppressor genes CASP8, RASSF1, MGMT, MSH6, GATA5, ATM1, TP53, and CADM1. miRNAs were identified with microarray screening, as well as selected samples, were tested for their mRNA expression levels. CASP8, RASSF1 were the most frequently methylated genes in all tumor samples. Simultaneous methylation of genes manifested significant results with respect to tumor staging, tumor type, and the differentiation of tumor and control samples. There was no significant dependence observed with the methylation of one gene promoter, rather with the simultaneous presence of all detected methylated genes' promoters. miRNA expression was found to be correlated to gene methylation. Epigenetic regulation appears to be of major importance in tumor progression and pathophysiology, making it an imperative field of study.

Keywords: childhood CNS tumors; mRNA; methylation; miRNA; microarray.