# Elucidating the mechanism and consequences of aberrant cyclin D1 gene expression

> **NIH NIH R01** · BUTLER UNIVERSITY · 2021 · $272,041

## Abstract

ABSTRACT
Some genes take drastic measures to force their aberrant expression. As an example, the gene cyclin D1
which is not normally present in B-cell lymphocytes is expressed in the blood cancer Mantle Cell Lymphoma
(MCL). MCL is the most aggressive of all B-cell malignancies and a chromosomal translocation event, that
pre-dates the disease, activates the cyclin D1 promoter is the initiating lesion in the transformation of normal
B-cells. Once expressed, the transcribed cyclin D1 message (pre-mRNA) undergoes further processing
which enables it to shorten it's 3'untraslated region (3'UTR) thus increasing the half-life of the transcript.
The expression of cyclin D1 in MCL facilitates a hyper-proliferative phenotype and increases the genetic
instability and chromosomal abnormalities of B-cells. In our prior work we identified a novel fusion gene in
MCL cell lines and patient samples where cyclin D1 is joined to another gene thus resulting in a truncated
3'UTR. The goal of this project is to determine the molecular mechanisms that drive the shortening of the
3'UTR of cyclin D1 as well as the effects of the cyclin D1 driven chromosomal translocation events. In this
proposal we will determine how the sequences found in the pre-mRNA of cyclin D1 as well as proteins
involved in 3'end processing play a role in optimizing the expression of cyclin D1 in MCL (Aim 1). We will
also systematically identify fusion genes, which result from chromosomal translocation events, using third
generation sequencing technology which allows us to get full length gene transcripts (Aim 2). Although
chromosomal translocations are known to occur with a high degree of frequency in MCL, apart from
serendipity discovery in individual case studies, little effort has been put into identifying fusion genes on a
global scale making this type of research innovative. Furthermore, our study will determine the molecular
basis of abnormal 3'end formation will answer a basic question in the field. This will have a positive impact
by establishing better understanding of disease causing genes are expressed in human cells and will allow
for more effective strategies to detect and treat disease.

## Key facts

- **NIH application ID:** 10225987
- **Project number:** 5R01GM135361-02
- **Recipient organization:** BUTLER UNIVERSITY
- **Principal Investigator:** Chioniso Patience Masamha
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $272,041
- **Award type:** 5
- **Project period:** 2020-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10225987

## Citation

> US National Institutes of Health, RePORTER application 10225987, Elucidating the mechanism and consequences of aberrant cyclin D1 gene expression (5R01GM135361-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10225987. Licensed CC0.

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