Abbreviated Name

Markowitz Supplement 2012

Lead Investigator

Markowitz, Sanford — Case Western Reserve University

Coordinating Investigator

No coordinating investigator

Involved Investigators

• Markowitz, Sanford — Case Western Reserve University

Abstract

No abstract availalbe.

Aims

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.

Analytic Method

No analytic method available.

Publications

• No publications available at this time for this protocol.

Biomarkers

• No biomarkers available at this time for this protocol.

Data Collections

• No data collections available at this time for this protocol.

 Team Project

Start Date

Jul 1 2012

Estimated Finish Date

Jun 30 2013

Protocol ID

363

Protocol Type

Single

Fields of Research

• Genomics

Collaborative Group

G.I. and Other Associated Cancers Research Group

Cancer Types

• Malignant neoplasm of colon