# Detection of microsatellite instability biomarkers for therapeutic clinical trial eligibility

> **NIH NIH UH3** · OHIO STATE UNIVERSITY · 2021 · $314,062

## Abstract

When enrolling patients with advanced cancer in clinical trials, there is a need for clinical grade diagnostics to
detect predictive biomarkers for novel immunotherapies. Microsatellite instability (MSI) has been identified as a
novel predictive biomarker for cancer immunotherapy. Detecting MSI is currently accomplished with multiple
redundant assays including immunohistochemistry for four proteins in the DNA repair pathway (MLH1, MSH2,
MSH6, PMS2) and PCR for five selected microsatellite positions on finite tumor specimens (2). These
diagnostic tests have been optimized for patients with colorectal cancer suspected of having germline Lynch
Syndrome. Unfortunately, these assays oftentimes exhaust finite clinical specimens. The use of next
generation sequencing (NGS)-based tests has expanded the profile of molecular diagnostics and raises the
potential to integrate detection of MSI and eliminate the requirement for multiple parallel tests. While patients
undergo genomic testing for other types of mutations such as point mutations, there is a critical need to
augment current assays to include detection of microsatellite instability given its predictive value. Furthermore,
current microsatellite detection algorithms have been specifically developed for a small number of cancer types
and therefore are not accurate for MSI testing in most cancers. Our Clinical Laboratory Improvement
Amendments (CLIA)--compliant Cancer Genomics Lab has extensive experience in developing clinical grade
tumor sequencing, bioinformatics, and mutation-driven trials (3-6). We hypothesize that targeted DNA
sequencing and analysis enables the detection of microsatellite instability in patient specimens from
diverse cancer types. During the UH2 Phase of Analytic Validation, we will determine the sensitivity,
specificity, reproducibility and reportable ranges of a targeted DNA microsatellite sequencing assay, MSI-Dx,
utilizing clinical tumor specimens (Aim 1). We will demonstrate scalability, rapid turnaround, and use of MSI-Dx
on a desktop sequencer. During the UH3 Phase of Clinical Validation, the MSI-Dx assay will be applied on a
diverse collection of samples comprised of known MSI-H tumors including colorectal, endometrial, and other
cancer types (Aim 2). Further, we will utilize the MSI-Dx assay for patients enrolled in a real time clinical tumor
sequencing study (Aim 3). Importantly, MSI-Dx can be integrated with other NGS-based testing strategies. This
assay will have a broad therapeutic impact by facilitating precision medicine clinical trials for patients with
MSI-H tumors.

## Key facts

- **NIH application ID:** 10128404
- **Project number:** 5UH3CA216432-04
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Sameek Roychowdhury
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $314,062
- **Award type:** 5
- **Project period:** 2017-09-25 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10128404

## Citation

> US National Institutes of Health, RePORTER application 10128404, Detection of microsatellite instability biomarkers for therapeutic clinical trial eligibility (5UH3CA216432-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10128404. Licensed CC0.

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