# Contribution of Epigenome to PRKCI-Driven High-Grade Serous Ovarian Cancer

> **NIH NIH R21** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2021 · $416,543

## Abstract

ABSTRACT
Cancer cells acquire genetic and epigenetic alterations that increase fitness and drive progression through
multiple steps of tumor evolution. Recent studies have vastly enhanced our understanding of the genetic
events in high-grade serous ovarian cancer (HGSOC), - the most prevalent and lethal form of epithelial ovarian
cancer. However, we do not have complete understanding of driver epigenetic alterations that are associated
with tumor progression in this disease. In HGSOC, somatic mutations - other than those on P53 - remain
uncommon and inter-tumor heterogeneity is high suggesting other genetic or epigenetic events may be primary
drivers of the disease. Focusing on a highly prevalent copy number gain of 3q26 locus (~70%) that harbors a
potent oncogene PRKCI in conjunction with p53 mutations, we have developed a genetically engineered
mouse model of HGSOC. We demonstrated that PRKCI is highly oncogenic in serous ovarian cancer and
modulates tumor microenvironment via regulation of immune genes. Our preliminary experiment identified
several epigenetic proteins as PRKCI interactors including SMARCA5, MLL5, BAZ2B, MAEL and BCOR
suggesting that PRKCI may modulate epigenome. Therefore, we hypothesize that PRKCI amplification and
TP53 mutations together set-up specific chromatin states that drive tumorigenesis in ovarian cancer.
We further suggest that these epigenomic aberrations can provide specific vulnerabilities for targeted
therapies. The objective of this proposal is to identify such chromatin states associated with ovarian cancer
progression in specific genetic context of PRKCI or 3q26 amplification and P53 mutation, determine their
functional nature and determine the role of PRKCI-interacting chromatin regulators. In aim 1, we will determine
the chromatin states in PRKCI overexpressing and P53 mutant serous ovarian epithelium from a genetically
engineered mouse model as well as human tumors. In aim 2, we will study contributions of SMARCA5 in
PRKCI-mediated epigenome reprogramming and cellular phenotypes in ovarian tumorigenesis. Overall,
motivated from the concept of precision medicine, our proposal is focused on identifying epigenomic alterations
and vulnerabilities in ovarian cancers that harbor PRKCI overexpression or 3q26 amplification and P53
mutation.
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## Key facts

- **NIH application ID:** 10112045
- **Project number:** 1R21CA256278-01
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Kunal Rai
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $416,543
- **Award type:** 1
- **Project period:** 2021-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10112045

## Citation

> US National Institutes of Health, RePORTER application 10112045, Contribution of Epigenome to PRKCI-Driven High-Grade Serous Ovarian Cancer (1R21CA256278-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10112045. Licensed CC0.

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