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You are here: Home › Protocols › Targeted Sequencing for Discovery and Validation of DNA Methylation Markers of Colon Cancer Metastasis

Targeted Sequencing for Discovery and Validation of DNA Methylation Markers of Colon Cancer Metastasis

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No coordinating investigator defined.

No involved investigator sites defined.

Genomics
G.I. and Other Associated Cancers Research Group

Colon cancer is the second leading cause of cancer death in the United States. A key issue in treating colon cancer patients is inability to accurately predict tumors that have metastatic potential and require adjuvant chemotherapy. This project will test the model that tumor metastases arise from intra-tumor heterogeneity generated by DNA methylation events, and that detecting these events can provide a predictve signature of tumors with poor outcome


The specific aims of this study are to determine whether in human colon cancer epigenetic gene silencing by aberrant DNA methylation provides the basis for intra-tumor heterogeneity and generation of lethal metastasis. We will answer this question by: 2.1. Comprehensive NextGeneration sequencing based analysis of DNA methylation across promoter associated CpG islands will be used to compare the DNA methylome of 20 colon cancer hepatic metastases versus 20 matched primary colon cancer tumors. 2.2. Sequence comparisons of the DNA methylome between matched colon cancer hepatic metastases and colon cancer primary tumors will be analyzed to identify presence or absence of metastases specific DNA methylation signatures, and to determine whether metastases are clonally identical to colon cancer primaries, are generated from subclones within colon cancer primaries, or are generated from subclones that arise in blood or distant sites outside of colon cancer primaries. Methyl-BEAMing based assays will be used to confirm the presence or absence within colon cancer primaries of subclones bearing DNA methylation signatures that typify the metastatic lesions, but are divergent from the dominant signature of tumor primaries. 2.3. The predictive potential of metastases associated methylation marks will be tested by determining the frequency of these aberrant methylation marks in a validation cohort of over 700 colon cancer tissue specimens from early stage colon cancer primaries, late stage colon cancer primaries, and colon cancer hepatic metastases.

There are currently no biomarkers annotated for this protocol.

No datasets are currently associated with this protocol.


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