Epigenetic Profiling of Human Colorectal Cancer

DNA methylation, together with chromatin modifications, constitute the epigenome that functions to regulate gene expression and genome integrity. DNA methylation alterations are ubiquitous in human cancers, as many genes acquire DNA methylation in a cancer-specific manner. DNA methylation at these sites in the genome of cancer cells not only serves as a marker for tumor identification, but together with gene mutation and gene expression data, can also be used to describe subsets of tumors of the same organ source. We have previously shown distinct human colorectal cancer subtypes based on DNA methylation differences. Correlating these DNA methylation differences with clinical co-variates will serve to further understand how these distinct subtypes are generated. We have collected 100 colorectal tumor tissues (for which clinical information is known) and have obtained (unprotected) genome-wide DNA methylation and chromatin modification information for each sample for the purposes of identifying and classifying unique tumor subtypes of colorectal cancers. In addition, we have determined mutations of key genes relevant to colorectal cancer as well as gene expression profiles. We will use the clinical data for each de-identified sample to correlate with the DNA methylation, mutation and gene expression information so as to understand the driving forces behind these distinct colorectal subtypes. We have selected the most promising tumors for whole-genome bisulfite sequencing using next-generation sequencing technology to obtain complete maps of colon cancer methylomes. Researchers will be unable to identify the subjects because the samples and associated information have been de-identified and anonymized by the tissue source site. In addition, upon receipt by the USC Epigenome Center, we have assigned new random identifiers for each sample. The data generated using these new codes are not traceable to the patient identity.]]>
Letter of Information and Consent FormTumors were obtained from the Ontario Tumor Bank (within the Ontario Institute for Cancer Research, Ontario, Canada) with available clinical information including tumor stage and grade, patient age, and the results of surgery and/or of chemotherapy.]]>
December 2007: Received approval of USC Health Sciences Institutional Review Board to use Ontario Tumor Bank colorectal tumor samples for DNA methylation and gene expression profiling. March 2009: Received approval of Ontario Cancer Research Ethics Board to sequence individual samples using Whole-genome bisulfite-seq and deposit data in dbGaP. April 2011: Received approval of Ontario Cancer Research Ethics Board and USC Health Sciences Institutional Review Board to continue Bisulfite-sequencing until March 2012.]]>