# Delineating chromatin-related gene expression signatures as a function of HNSCC progression

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2021 · $550,112

## Abstract

Summary
Oral squamous cell carcinoma (OSCC), the most common subtype of head and neck carcinoma (HNSCC), has
very few targeted therapies available and poor overall survival. Novel strategies based on the high-throughput
analyses offer new hope for improved risk assessment, early cancer detection, therapeutic intervention and
tumor surveillance, but the impact of these strategies has been limited by an incomplete understanding of the
biology of oral cancer, particularly in its early developmental stages. Like other solid malignancies, OSCCs begin
as pre-neoplastic cellular proliferation that are driven by the serial acquisition of genetic and epigenetic
alterations. Nearly 20% of patients with OSCC harbor multiple pre-malignant lesions showing signs of dysplasia,
often visually identified as leukoplakia or erythroplakia. As some of these lesions evolve to malignant neoplasms,
they represent intermediate steps in OSCC progression. This multi-step process from normal epithelium to early
premalignant change to carcinoma in situ (CIS) and fully invasive carcinoma, provides a rational framework for
studying molecular alterations underlying the OSCC progression. However, relatively few oncogenic mutations
critical to the development of OSCC are currently recognized, impeding discovery of novel targeted therapeutics.
Moreover, mutations alone are insufficient to explain the broad spectrum of gene expression changes that
characterize OSCC.
Whole-genome distribution of enhancers, the functional elements of the chromatin, is associated with the
development of multiple solid malignancies, and mediates widespread genomic changes including expression
of known cancer driver genes. Although it is becoming apparent that enhancers are the critical regulators of their
target genes, and enhancer genomic elements are rapidly emerging as potent targets for anti-cancer
therapeutics, the association between chromatin modifications and gene expression patterns in OSCC is not yet
defined, and no comprehensive molecular information is available in oral pre-neoplastic lesions. This project will
use novel bioinformatics and experimental approaches to test the central hypothesis that transcriptional changes,
which arise during OSCC carcinogenesis, are enabled by dynamic chromatin alterations. Our integrated analysis
will couple the gene expression and methylation landscape with a corresponding evaluation of the cancer-
specific enhancer phenotype throughout the continuum of OSCC progression. Characterizing the timing and
manner by which gene expression alterations coincide with markers of chromatin organization in sequentially
progressive lesions within the oral cavity (e.g. mild dysplasia, moderate dysplasia, severe dysplasia/CIS, and
invasive OSCC) will yield the first comprehensive epigenetic map of HNSCC evolution, and will define the key
epigenetically regulated genes that drive OSCC carcinogenesis. Furthermore, evaluating their biological and
clinical relevance may open...

## Key facts

- **NIH application ID:** 10131189
- **Project number:** 5R01DE027809-04
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Daria A Gaykalova
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $550,112
- **Award type:** 5
- **Project period:** 2020-09-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10131189

## Citation

> US National Institutes of Health, RePORTER application 10131189, Delineating chromatin-related gene expression signatures as a function of HNSCC progression (5R01DE027809-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10131189. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*