# The role and mechanism of alternative RNA splice variants and gene fusions as drivers of cancer

> **NIH NIH R35** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2021 · $485,162

## Abstract

Abstract
My lab has been the leader in the field of mouse modeling for brain tumors over the past 15 years. We have
developed a suite of genetically engineered mouse models that are demonstrably representative of human
gliomas and other tumor types. These models have been used to inform treatment options for clinical agents,
and this now enables us to propose these models are suitable testbeds for testing potential major improvements
to how these diseases are treated. We have three projects. 1) We are understanding the central role of specific
splice variants of TrkB in embryonic development and oncogenesis throughout the body. The RCAS modeling
system has been used here to show that forced expression of the embryonic splice variant in adult tissues
leads to cancer formation broadly. In this project we will investigate the mechanisms of oncogenesis for this
splice variant and determine if it could be a good diagnostic or therapeutic target. 2) We are now using the
modeling system developed for glioma to address the biology of rare tumors driven by gene fusions. In this
grant we propose to understand the mechanisms of oncogenesis for YAP1 gene fusions in the rare tumors
ependymoma, porocarcinoma and aggressive meningioma (all for which we have YAP1 gene fusion driven
models currently). 3) And, we will use these mouse models to study therapeutic response and identify
therapeutic strategies for these fusion driven tumors including identification of FDA approved drugs that would
intervene downstream of the action of the gene fusion.

## Key facts

- **NIH application ID:** 10294170
- **Project number:** 1R35CA253119-01A1
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** Eric C. Holland
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $485,162
- **Award type:** 1
- **Project period:** 2021-09-21 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10294170

## Citation

> US National Institutes of Health, RePORTER application 10294170, The role and mechanism of alternative RNA splice variants and gene fusions as drivers of cancer (1R35CA253119-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10294170. Licensed CC0.

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