# Polyploidy and Sex Dimorphism in a Drosophila Tumor Model

> **NIH NIH R01** · TULANE UNIVERSITY OF LOUISIANA · 2024 · $341,248

## Abstract

Project Summary
Ploidy variation is a cancer hallmark and is frequently associated with poor prognosis in high-grade cancers.
Such variation can include an increase in chromosome set (polyploidy), a difference of chromosomes in a
set (aneuploidy), or regional ploidy changes and copy number variations (CNVs). Genome-wide studies of
multiple cancer specimens have shown that whole genome doubling is one of the most common molecular
abnormalities in human cancers and is closely linked to other copy number alterations. However, how
exactly polyploidy contributes to tumor growth, progression and malignancy remains largely unclear. Using
a simple and highly reproducible Drosophila tumor model, where an active form of Notch (NICD) drives
tumorigenesis in an epithelial transition zone (TZ), our preliminary studies indicate that tumor progression is
driven by occurrences of polyploid mitosis, endoreplication, and ploidy reduction divisions. Both polyploid
mitosis and depolyploidization are error-prone and can lead to chromosome abnormalities such as CNVs
and polyaneuploidy, resulting in intratumoral heterogeneity in DNA ploidy. Comparative RNA-Seq analyses
revealed that DNA damage response (DDR) genes are upregulated in these NICD-TZ tumors. Genetic
epistasis studies have further shown that some of these DDR genes are required for the ploidy reduction
division. Additionally, these tumors show sexual dimorphism regarding tumor growth and progression.
Based on these findings, we hypothesize that polyploidy and associated cell-cycle variants are critical for
continued tumor growth and increased tumor-cell genome instability during tumor progression. To test this
hypothesis, we will carry out studies proposed in the following two aims: (1) to determine how polyploid cell
divisions contribute to tumor growth and progression; (2) to characterize the sexual dimorphism of the
NICD-TZ tumor model. The successful execution of the proposed studies will lead to a better
understanding of intratumor ploidy heterogeneity and cancer evolution, as well as improved strategies in
cancer prevention and treatment in a sex-dependent manner.

## Key facts

- **NIH application ID:** 10999201
- **Project number:** 1R01CA287524-01A1
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** Wu-Min Deng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $341,248
- **Award type:** 1
- **Project period:** 2024-08-01 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10999201

## Citation

> US National Institutes of Health, RePORTER application 10999201, Polyploidy and Sex Dimorphism in a Drosophila Tumor Model (1R01CA287524-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10999201. Licensed CC0.

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