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
There are currently no biomarkers annotated for this protocol.
No datasets are currently associated with this protocol.
The National Cancer Institute's Division of Cancer Prevention has released a new funding opportunity to solicit organ-specific applications for Biomarker Developmental Laboratories (BDLs), one of the four scientific units of the recently funded Early Detection Research Network (EDRN). The EDRN is a national infrastructure funded to discover, develop, and validate biomarkers for risk assessment, detection, and molecular diagnosis and prognosis of early cancer. BDLs are responsible for the discovery, development, characterization, and testing of new, or the refinement of existing, biomarkers and biomarker assays for risk assessment, detection, and molecular diagnosis and prognosis of cancers.
The existing BDLs are primarily focused on ovary and gastrointestinal cancers. The proposed BDLs (to be supported under this funding opportunity) should be focused on one or more of the following cancers: breast, prostate and other genitourinary organs, or lung. In addition, cancers with rapidly rising incidence rates, e.g., endometrial, hepatocellular, kidney, thyroid, oropharyngeal cancers, and/or cancers with unique etiology, e.g., mesothelioma, will be considered.
The newly funded units of the Early Detection Research Network will be announced later in April. Successful applicants have already been notified. Those researchers who were not successful during the last round of applications are encouraged to apply to this opportunity.