Differential Methylation of Sonic Hedgehog Pathway Genes in Acute Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia (ALL) is one of the most common childhood malignancies, which due to current therapeutic techniques, has one of the highest cure rates of any cancer (approximately 90%). Though ALL is closely associated with certain chromosomal translocations and resulting fusion proteins, such as TEL-AML1, it is widely held that changes in DNA methylation in the promoters of certain genes leading to inappropriate protein expression likely play a role in increasing disease severity. Examples of such proteins are those involved in Sonic hedgehog signaling, which has been found to be inappropriately active in several cancer types. In this study, methylation patterns of 84 genes involved in the Sonic Hedgehog pathway were examined in 17 ALL patients and 13 control samples, with five 1000 bp regions corresponding to the genes\u27 promoters being the primary sites of interest. Forty-five genes displayed definitive methylation alterations in at least one of these regions, and one gene, IFT52, displayed differential methylation in all five regions. Further studies will be needed to determine if this differential methylation is causing alterations in protein expression