Aberrant DNA methylation in Ewing sarcoma.

Epigenetics are types of mechanisms that that occur in a cell that do not permanently alter the DNA code but can contribute to the regulation of genes. DNA methylation is part of a complex mechanism that affects the chromosomal structure of a gene. It is known that aberrant DNA methylation occurs in cancer cells and can silence genes that would normally prevent cancer formation. Hypermethylation of these "tumor suppressor genes" has been shown to affect nearly all adult and pediatric cancers. However, we do not know how DNA methylation contributes to the malignancy of Ewing sarcoma (ES), a type of bone cancer that affects teenagers and young adults. The goal of this research proposal is to use state of the art technology to identify genes that are "turned off" by DNA methylation and contribute to ES tumor formation. We will identify genes hypermethylated in ES tumors, but not in normal cells, and determine if the methylation pattern of these genes is associated with clinical or pathological features of the tumors, such as location of the primary tumor, whether or not the cancer had spread to other parts of the body when discovered, and how the tumor responded to treatment. We also will find out if DNA methylation is associated with other genetic defects identified in ES tumors, such as loss of the tumor suppressor p16/CDKN2A. We hope that this study will lead us to better understanding of the cause of ES and will lead to the development of better treatments.