Abstract
Establish the role epigenetic methylation plays in the segregation of Medulloblastoma subgroups, through pathway analysis in the literature and cancer genome Atlas publicly available data. The goal is to develop an in-vitro assay to study therapeutic responses for subgroups 3 and 4. Functional analysis assays will be used to determine a mechanism for chemoresistance in specific subgroups. In the current study, we assessed Medulloblastoma group 3 (D341) and Group 4 (D283) cell lines using the DNA isolation kit and angiogenesis kits which allows for amplification via PCR and visualize tube formation for tumor nutrients. Twist 1 fended were measured and recorded with the methylation Gold. Group 3 MB cell lines treated with chemotherapy reagents demonstrate altered methylation profiles, angiogenic tube formation increase, a decrease in apoptosis, and underwent phenotypic changes to overcome resistance. Gel electrophoresis results indicated consistent Twist-1 expression in the DAOY+cisplatin cell line in comparison to the control. Cells treated with chemotherapeutic agents evade the mechanisms of apoptosis resulting in angiogenesis. We identified a possible correlation between cisplatin treatment, alteration of methylation patterns, and an increase of Twist-1 gene expression. Twist-1 previously identified to be involved in angiogenesis and cisplatin resistance (Roberts et al. 2016), this supports our hypothesis that alterations in methylation patterns result in an increase in overall chemoresistance.
Highlights
Medulloblastoma (MB) is the most common malignant brain tumor of childhood, and it accounts for about 20 percent of all childhood brain tumors [23]
Our results indicate that Group 3 MB cell lines treated with chemotherapy reagents have altered methylation profiles, avert apoptosis, and undergo phenotypic changes to overcome resistance
This suggests that cisplatin treatment results in the alteration of the methylation patterns of the cancer cell DNA
Summary
Medulloblastoma (MB) is the most common malignant brain tumor of childhood, and it accounts for about 20 percent of all childhood brain tumors [23]. Survival rates in children vary depending on the patient’s age and how much the tumor spreads. Treatment options for this tumor consist of neurosurgery, craniospinal radiation, and chemotherapy [10]. Many patients become resistant or are intrinsically resistant to treatment [2]. A better understanding of the molecular biology of the tumor is essential. There are four subtypes that have been identified in children with medulloblastoma, WNT-activated, SHHactivated, Group 3 (non-WNT / non-SHH), and Group 4
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