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Team Project

Preliminary Validation of Biomarkers for the Detection of Colorectal Adenomas (Team Project #1)

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Brenner, DeanUniversity of Michigan
Brenner, DeanUniversity of Michigan
EVL, ITGA4 MGMT, EVL, ITGA4, and CDKN2A, 2) genes that are not subject to methylation in colon cancer: GSTP1, BRCA1, and CDH1, and 3) genes that undergo aging related methylation in the colon: ESR1, MYOD1, and N33 Getzenberg CCSA-2
Hypermethylation
Genomics
Proteomics
Glycomics
G.I. and Other Associated Cancers Research Group
1

the goal of identifying those biomarkers developed by the GI collaborative that will predict the presence of advanced colorectal adenomas.

We propose a GI Collaborative biomarker validation project with the goal of identifying those biomarkers developed by the GI collaborative that will predict the presence of advanced colorectal adenomas. Biomarkers from the diverse colon focused and pancreatic focused BDLs of the GI Collaborative will assay their biomarkers on sets of identical reference set samples. The GI Collaborative will also assess markers of tissue/serum-plasma and/or urine from other EDRN collaborative groups, i.e. urologic, breast, lung, in this reference set. The most promising biomarkers that meet required adenoma detection bars will be assayed in a second, blinded test set of biosamples from a separate group of subjects before being considered for inclusion in large, cross sectional biomarker validation project for the early detection of both colorectal adenocarcinomas and advanced adenomas. Aim 1 To define preliminary sensitivity, specificity, and their variance of biomarkers for the detection of advanced adenomas in a standardized, open labeled training biosample reference set. Aim 2 To select those biomarkers for the detection of advanced adenomas in the training set for additional validation in a standardized biosample reference test set using pre-set performance characteristics. Aim 3 To verify sensitivity, specificity, and their variance of biomarkers for the detection of advanced adenomas in a standardized, blinded test biosample reference set. Aim 4 To select biomarkers for the detection of advanced adenomas from the test set for inclusion in a large, cross sectional validation trial of biomarkers for the early detection of advanced adenomas.
Markowitz Approach: Candidate aberrant methylated loci will be identified from RRBS analysis of tissues in the archive of the Case Medical Center. Real-time MS-PCR assays will be developed to quantitatively assay for these aberrant methylation events. Validation of these methylation events, their timing, and their selectivity for neoplasia, will be examined in tissue samples from the GLNE archive including normal mucosal biopsy from individuals with clean colonoscopies, normal mucosal biopsies from individuals with colon neoplasia (advanced adenomas or cancers), biopsies of non-advanced adenomas, biopsies of advanced adenomas, biopsies of early stage colon cancers, and biopsies of late stage colon cancers. Marker loci that show sensitivity and specificity for colon neoplasia at the independent tissue collections of the GLNE will be tested for their sensitivity and specificity for early and late neoplasia detection in body fluids including in fecal DNAs and in plasma samples. Grady Approach: Quantitative CpG methylation assessment with quantitative methylation specific PCR (qMSP or MethyLight). Lampe compare protein expression/activation in adenoma vs. normal colon mucosa via antibody array to discover diagnostic/prognostic biomarkers. The best diagnostic and prognostic markers will then be rescreened on a tissue microarrays. After triage, we will determine whether the surviving biomarkers are adenoma or stromal derived by analyzing its expression pattern. Getzenberg evaluate the potential of CKB IHC staining within the colon to serve as a marker for the development of colon cancer and perhaps at the onset of adenomas. The laboratory is now developing a sandwich ELISA to detect CCSA-2 in the serum and would propose to evaluate this marker

No datasets are currently associated with this protocol.


Announcement 10/23/2017

Three new FOAs on the Human Tumor Atlas and associated with the Cancer Moonshot Initiative have been released. Please click here for more information.

32nd SC Meeting
Thank you to everyone who made the 32nd EDRN Steering Committee meeting a success. The next event is the 10th EDRN Scientific Workshop from March 6-8, 2018 in Bethesda, MD. More information about this Workshop will be sent soon. Click here to view the flyer.
EDRN Founder Honored

Dr. Sudhir Srivastava was honored with the Distinguished Service Award from the American Pancreatic Association at the group's annual meeting this year, for his outstanding commitment to pancreatology.