# (PQ6) Radiogenomics of colorectal polyps to assess benign proliferative vs. premalignant states.

> **NIH NIH R01** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2021 · $491,493

## Abstract

SUMMARY
Colorectal cancer (CRC) is consequence of molecular alterations transforming normal epithelial cells into their
neoplastic counterparts. Virtually, all CRCs derive from adenomas or serrated polyps, which begin forming in
adulthood, and lead to cancer in 6-7% of the U.S. population by 80 years of age. However, since 30-50% or
more of the population is affected by colon polyps, it is apparent that the vast majority of these lesions do not
progress to CRC, but rather are benign proliferative lesions and not truly premalignant lesions. The
molecular mechanisms that dictate which polyps are “benign proliferative disease” and which are
“premalignant states” are essentially unknown. We propose to use an exceptional and unique clinical
resource to determine whether the underlying genetic alteration profile, gene expression status, and/or
epigenetic state of an early polyp governs its fate, using in vivo growth rate as a surrogate measure of
malignant potential. The exceptional and unique resource that will permit us to do these studies is a large
series of human colorectal polyps whose volumetric growth patterns have been serially assessed over time by
CT colonography (CTC) prior to resection. In addition, volumetric textural analysis of CTC polyp data, which
can be used to distinguish non-neoplastic proliferative lesions (hyperplastic polyps) from adenomas, will be
correlated with growth rates. We will correlate results from whole exome sequencing, gene expression studies,
and high-density methylation arrays with the observed CTC-based volumetric growth patterns, textural analysis
and polyp histology.
This “radiogenomic” analysis of our series of benign and premalignant polyps will then allow us to test an
innovative hypothesis about the mechanism(s) that determines a polyp’s fate. We have previously shown that
many mutations and epigenetic alterations arise very early in polyp formation (the “Big Bang” hypothesis of
tumorigenesis) rather than sequentially, and that the initial tumor profile governs whether the polyp is
premalignant or benign. Thus, some polyps might be “born to be bad”. In this proposal, we will test the novel
hypothesis that the genetic, transcriptional, or epigenetic state established at polyp formation dictates if a polyp
is a benign proliferative lesion or a premalignant state. Our SPECIFIC AIMS are:
1. To fully assess CTC data from a large cohort of patients with colorectal polyps that were followed in vivo by
serial CTC prior to colonoscopic resection to accurately establish polyp growth rates and texture;
2. To determine whether mutations or transcriptional changes that occur early in tumorigenesis dictate polyp
fate; and
3. To determine whether the epigenotype of a polyp correlates with growth behavior and the potential to
become a CRC.

## Key facts

- **NIH application ID:** 10228657
- **Project number:** 5R01CA220004-05
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** William Mallory Grady
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $491,493
- **Award type:** 5
- **Project period:** 2017-09-21 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10228657

## Citation

> US National Institutes of Health, RePORTER application 10228657, (PQ6) Radiogenomics of colorectal polyps to assess benign proliferative vs. premalignant states. (5R01CA220004-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10228657. Licensed CC0.

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