Cancer-specific and tissue-specific differential DNA methylation analysis

Jeffrey Long, Graduate Student, Biomolecular Engineering
Monday, June 18, 2012, 1:00 PM to 3:00 PM
Location: Engineering 2, Room 506
Hosted By David Haussler

Abstract

Cancer is a pervasive disease characterized by failure of genetic and epigenetic mechanisms. Epigenetic mechanisms include DNA methylation, chromatin modification/interaction, and histone occupancy. These mechanisms have been shown to be implicated in transcriptional regulation of cancer genes, and as a consequence are believed to be a major factor in tumorigenesis, tumor growth and cancer progression. In particular hypermethylation of promoters has been associated with silencing of tumor suppressors, upregulation of oncogene transcripts as well as promoter switching. Furthermore, these phenomena have been observed repeatedly for genes in multiple tumor types suggesting that regulation of specific cancer genes by DNA methylation is common to multiple tumor types.

The conclusions from many studies have been that multiple tumor types share some common features, yet also have unique tissue-specific characteristics. However, testing the hypothesis that tumors have common differential methylation patterns has been limited by low resolution of methylation detection or interrogation of few cancer types. Similarly, expression analyses across multiple cancer types have been limited by array-based assays.

The afore mentioned limitations have recently been overcome by the ENCODE Consortium. Genome-wide methylation data such as reduced representation bisulfite sequencing for a diverse set of cells from normal and tumor tissue gives unselected (not microarray-based) single nucleotide level methylation status. Bisulfite sequencing is held to be the gold-standard of DNA methylation assays.

In this work we will test the hypothesis that analyzing cancer cell lines will help us determine cancer genes that are regulated by hypermethylation in common tumors.