# DNA Methylation and gene expression variations influence pituitary adenoma hormonal function and invasive growth

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $525,099

## Abstract

Project Summary: DNA Methylation and gene expression variations influence pituitary adenoma
hormonal function and invasive growth
Pituitary Adenomas (PAs) are among the most common intracranial tumors, and may cause
hypopituitarism, neurological deficits, and lethal hormonal oversecretion disorders such as Cushing's
disease and acromegaly. Although typically benign, PA invasion into surrounding dura, bone, and brain
is evident in nearly half of symptomatic patients and is the major barrier to achieving long-term tumor
control, hormonal remission, and normalized patient survival. Genetic mutations do not play a major
role in the development or behavior of non-familial PAs, and a major knowledge gap exists in
understanding the molecular underpinnings of PA hormonal function and invasive growth. Alternatively,
epigenetic (e.g., DNA methylation) and gene expression alterations are known to influence PA
phenotype, but these effects vary with gene location and context. Our team performed the first
epigenome-wide pilot study to explore the association of DNA methylation and gene expression with
PA behavior, and validated several genes implicated in PA hormonal function and invasion. Using a
similar workflow, our overall goal is to define the role that DNA methylation and gene expression play in
PA hormonal secretion and invasion in a larger study stratified according to PA hormonal subtype and
invasion status. We hypothesize that: 1) variation in DNA methylation and expression is associated with
subtype-specific PA hormonal function and invasion; 2) DNA methylation and expression data can be
used to identify novel molecularly-defined PA classes and complement current PA diagnostic schemes;
and 3) modulated expression of prioritized genes of interest will affect PA hormonal secretion and
invasion in vitro. To test these hypotheses, we aim to: 1) use integrative epigenomic profiling and RNA
sequencing approaches to analyze surgically-resected invasive and noninvasive PAs derived from a
multi-institutional consortium, 2) discover novel molecularly-defined PA subtypes using DNA
methylation and gene expression analysis, followed by development of a molecularly-based
classification and unified diagnostic scheme, 3) identify candidate DNA methylation and gene
expression markers associated with PA hormonal secretion and invasion, 4) use established rat and
surgically-resected human PA primary cell lines to test hormonal secretion and invasion phenotypes
following modulation of expression of prioritized genes. Understanding the molecular pathways
associated with PA hormonal secretion and invasion will provide practitioners with more precise
diagnostic information and help to develop targeted drug therapies to curb or reverse PA hormonal
oversecretion and invasion, thereby improving patient quality of life and survival. Knowledge derived
from this study could help refractory PA patients by helping to mitigate lifelong risks associated with
chronic hormone oversec...

## Key facts

- **NIH application ID:** 9999533
- **Project number:** 5R01CA230328-03
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Gabriel Zada
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $525,099
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999533

## Citation

> US National Institutes of Health, RePORTER application 9999533, DNA Methylation and gene expression variations influence pituitary adenoma hormonal function and invasive growth (5R01CA230328-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9999533. Licensed CC0.

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