# Multi-site Gastrointestinal Cancer Detection by Stool DNA Methylation

> **NIH NIH R37** · MAYO CLINIC ROCHESTER · 2022 · $404,684

## Abstract

PROJECT SUMMARY/ABSTRACT:
Gastrointestinal (GI) malignancies lead cancer deaths worldwide, killing ~3 million annually. In the U.S., only
colorectal cancers (CRC) are screened. Other GI cancers are not screened due to lack of accurate tests or
because prevalence is deemed too low for cost-effective screening. Consequently, most patients with GI
cancers present at late-stage and cure rates remain abysmally low. Effective early detection is desperately
needed to improve outcomes. Our group was central in development and validation of the FDA-approved multi-
target stool DNA test for CRC screening. We have begun to expand this approach, showing feasibility to detect
supra-colonic GI cancers by stool DNA testing. However, it is critical for a non-invasive molecular test to
localize the site of a primary cancer (“site-prediction”). Key preliminary data suggest that this may now be
possible. First, we have completed rigorous next-generation sequencing to identify differentially methylated
regions (DMRs) which appear highly discriminant for universal and site-specific detection of GI cancers.
Second, we prioritized these DMRs by strict filtering criteria and performed a confirmatory study with statistical
cross-validation on an independent set of CRC, gastroesophageal and pancreatico-biliary cancer and normal
control tissues. This showed that a panel of 8 selected DMRs could distinguish cancer from normal (95%
accuracy) and assign organ site (94-95% accuracy for each category) with overall site-prediction accuracy of
these findings have been confirmed with novel DMRs assayed from stool specimens obtained
from CRC and pancreatic cancer patients and normal controls (30, each). Using a 2-stage analysis, cancers
were distinguished from controls at 90% specificity in the first stage. At stage 2, the markers accurately
classified CRCs from pancreatic cancers with 90% accuracy.
88%. Third,
It is now our central hypothesis that luminal and
ductal adenocarcinomas can be detected and localized by stool assay of universal and site-specific DMRs.
This raises 3 key questions: 1) will stool assay of our novel DMRs show the high overall cancer sensitivity
and the site-prediction we have seen in preliminary data; 2) will the DMRs be specific for cancer across a
wide patient demographic spectrum and in the setting of non-malignant GI diseases; and 3) can sensitivity and
specificity be improved by novel assay technology? These will be addressed in the following parallel,
integrated, but independent specific aims: 1) Assess panel sensitivity and site-prediction accuracy in
stool specimens for adenocarcinoma at esophageal, pancreatic and colorectal sites; 2) Confirm and
evaluate DMR specificity in stool; and 3) Optimize novel assay conditions and marker selection for
cancer detection and site-prediction at esophageal, pancreatic and colorectal sites. With our team's
strong track record, extensive stool archive, and unique access to a state-of-the art assay platform, we exp...

## Key facts

- **NIH application ID:** 10372020
- **Project number:** 5R37CA214679-05
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** John Kisiel
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $404,684
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10372020

## Citation

> US National Institutes of Health, RePORTER application 10372020, Multi-site Gastrointestinal Cancer Detection by Stool DNA Methylation (5R37CA214679-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10372020. Licensed CC0.

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