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Genomics and epigenetics: A study of ependymomas in pediatric patients

Monserrat Pérez-Ramírez¹, Alejo Justino Hernández-Jiménez², Armando Guerrero-Guerrero²

¹Unidad de Investigación Médica en Genética Humana, Hospital de Pediatría "Dr. Silvestre Frenk Freud", Centro Médico Nacional "Siglo XXI", IMSS, Av. Cuauhtémoc 330, Col. Doctores, Del. Cuauhtémoc, 06720 México D. F., Mexico; Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Avenida Ciudad Universitaria 3000, Coyoacán, 04360 México D.F., Mexico.

Clinical Neurology and Neurosurgery

|March 14, 2016

Abstract

Objective:

We identify chromosomal alterations, the methylation pattern and gene expression changes in pediatric ependymomas.

Methods:

CGH microarray, methylation and gene expression were performed through the Agilent platform. The results were analyzed with the software MatLab, MapViewer, DAVID, GeneCards and Hippie.

Results:

Amplification was found in 14q32.33, 2p22.3 and 8p22, and deletion was found in 8p11.23-p11.22 and 1q21.3. We observed 42.387 CpG islands with changes in their methylation pattern, in which we found 272 genes involved in signaling pathways related to carcinogenesis. We found 481 genes with altered expression. The genes IMMT, JHDMD1D, ASAH1, ZWINT, IPO7, GNAO1 and CISD3 were found to be altered among the three levels.

Conclusion:

The 2p22.3, 8p11.23-p11.22 and 14q32.33 regions were identified as the most important; the changes in the methylation pattern related to cell cycle and cancer genes occurred in MIB2, FGF18 and ITIH5. The IPO7, GNAO1 and ASAH1 genes may play a major role in ependymoma development.

Keywords:

Cancer Genetic expression and chromosomal aberration Methylation Pediatric ependymoma

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Genomic DNA in Eukaryotes

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Eukaryotes have large genomes compared to prokaryotes. To fit their genomes into a cell, eukaryotic DNA is packaged extraordinarily tightly inside the nucleus. To achieve this, DNA is tightly wound around proteins called histones, which are packaged into nucleosomes that are joined by linker DNA and coil into chromatin fibers. Additional fibrous proteins further compact the chromatin, which is recognizable as chromosomes during certain phases of cell division.

Epigenetic Regulation

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...

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