# Identification and Clinical Validation of Key Transcription Factor Isoforms Linked to Breast and Prostate Cancer Subgroups using Epigenetic Traits

> **NIH NIH K01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $235,174

## Abstract

Identification and Clinical Validation of Key Transcription Factor Isoforms Linked to Breast
 and Prostate Cancer Subgroups using Epigenetic Traits
PROJECT SUMMARY/ABSTRACT
The clinical behavior and progression of breast and prostate cancers vary case by case, in large part due to
different characteristics of tumor subtypes. Clearly, different treatment regimens should be used to treat each
tumor subgroup. Therefore, a comprehensive understanding of the mechanisms and molecular features that
can distinguish tumor subgroups is of great importance, both for mechanistic insight and diagnostic/prognostic
utility. Regulatory elements such as promoters and enhancers contain multiple transcription factor (TF) binding
sites, which can alter expression of the genes they regulate. Of note, the active state of specific subsets of
regulatory elements annotated by epigenomic profiles is highly linked to cellular identity and is altered in
human diseases. I hypothesize that there are specific TFs differentially active in each breast and prostate
tumor subtype and that these TFs inappropriately activate a set of tumor-specific regulatory elements, leading
to altered expression of genes involved in disease phenotypes. To facilitate identifying the critical TFs linked to
activated regulatory elements in tumor tissue samples, I developed a method called TENET (Tracing Enhancer
Networks using Epigenetic Traits) that measures relationships (intra- and inter-chromosomal) between DNA
methylation levels at enhancers and expression levels of all human genes. I now propose to extend my
preliminary work by expanding the functionality of TENET such that I can include analysis of individual TF
isoforms linked to breast and prostate cancer subgroups. I will first begin by identifying TF isoforms and
activated regulatory elements, specific to each tumor subtype using epigenomic datasets from tissue samples
(Aim 1). I will then characterize the molecular function of several selected key TF isoforms linked to specific
tumor subtypes, mapping their binding sites and deciphering their target gene networks (Aim 2). Lastly, I will
prioritize TF isoforms related to cancer progression and outcome using tumor tissue datasets and cancer
patient information, in collaboration with clinicians (Aim 3).
During my K01 period, I will acquire advanced training in bioinformatics and molecular biology, and newly
explore translational genomics and precision medicine under the mentorship of Dr. Farnham and the other
members of my mentoring team who have expertise in DNA methylation and epigenomic analyses (Drs.
Berman, Carpten) and the biology of breast and prostate cancer and clinical translation (Drs. Press, Carpten,
and Goldkorn). I will also participate in career development opportunities at USC, which places a strong
emphasis on leadership and professional growth, hosting grant-writing, research funding strategy, responsible
conduct of research, management and ethics, and mentorship workshops...

## Key facts

- **NIH application ID:** 10000054
- **Project number:** 5K01CA229995-03
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Suhn Kyong Rhie
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $235,174
- **Award type:** 5
- **Project period:** 2018-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10000054

## Citation

> US National Institutes of Health, RePORTER application 10000054, Identification and Clinical Validation of Key Transcription Factor Isoforms Linked to Breast and Prostate Cancer Subgroups using Epigenetic Traits (5K01CA229995-03). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/10000054. Licensed CC0.

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