SIR Medicine Investigation Abstract
CPG METHYLATION ANALYSIS OF GENES WITHIN THE COMMONLY DELETED SEGMENT (CDS) OF 5Q31 IN THERAPY-RELATED MYELODYSPLASTIC SYNDROME/THERAPY-RELATED ACUTE MYELOID LEUKEMIA (T-MDS/T-AML)
Presenter:
Jaehee Chung, Illinois Mathematics and Science Academy
Advisor:
Dr. Michelle LeBeau, University of Chicago
Abstract:
Therapy-related myelodysplastic syndrome (t-MDS) and acute myeloid leukemia (t-AML) are late complications of cytotoxic therapy, for malignant diseases. Previous studies have identified a commonly deleted segment (CDS) of chromosome 5 in t-MDS/t-AML containing 21 genes. Eleven of the 21 genes contain CpG islands, possible sites of methylation. Hypermethylation can silence tumor-suppressor genes, whereas hypomethylation may lead to the expression of oncogenes. I hypothesize that hypermethylation of one or more of these islands in the remaining chromosome 5 homolog inactivates critical genes. This silencing of gene expression is a "second hit" to the CDS. Of the eleven CpG-containing genes, three have been examined for methylation activity. I plan to analyze the eight remaining genes, starting with HnRNPA0. By sequencing the DNA amplified from bisulfite-treated DNA, I differentiated between cytosines that are methylated and unmethylated. Thus far, I have mapped the methylated CpGs in the HnRNPA0 gene in a non-malignant lymphoblastoid cell line. Two CpGs were methylated in the tested regions, suggesting that HnRNPA0 is not silenced by methylation in this cell line. In future studies, I will examine HnRNPA0 methylation in leukemia cell lines and t-AML samples.