# Genomic and functional approaches to characterize Chr1q gains in cancer

> **NIH NIH R01** · YALE UNIVERSITY · 2024 · $301,500

## Abstract

Abstract
Chromosome gains and losses are found in nearly all human cancers. However, the functional importance of
these massive gene dosage imbalances remains poorly understood. Notably, large chromosomal segments are
technically challenging to manipulate, which has limited our ability to precisely model and interrogate the
consequences of specific aneuploidies. The relationship between aneuploidy and cancer development is of
particular importance for individuals with Trisomy 21/Down syndrome, as children with this condition exhibit a
150-fold increased risk of developing acute myeloid leukemia (AML).
In the parent grant for this application (1R01CA276666), we described a novel CRISPR-mediated chromosome
engineering methodology that allows us to eliminate specific aneuploid chromosomes from human cancer cells.
We proposed to apply this approach to interrogate the consequences of chromosome 1q aneuploidies in a
genetically-controlled setting. In this supplemental application, we plan to leverage these same chromosome
engineering techniques to study gains of chromosome 21 in leukemia. In particular, we will eliminate single
copies of chromosome 21 from human AML cell lines that are aneuploid for this chromosome, thereby creating
genetically-matched cells that are either disomic or trisomic for chromosome 21. We will then examine how loss
of the chromosome 21 trisomy impacts various cancer-related phenotypes, including gene expression, cell
fitness, and drug sensitivity. Additionally, we will over-express individual chromosome 21 genes in our
engineered chromosome 21-loss cell lines, which will allow us to identify specific genes encoded on this
chromosome that impact specific leukemic phenotypes. These assays will address the NCI’s INCLUDE program
goal of uncovering genetic factors associated with trisomy 21 that lead to the distinct biological and clinical
behavior of Down syndrome-associated leukemias.

## Key facts

- **NIH application ID:** 11010550
- **Project number:** 3R01CA276666-02S1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Jason Sheltzer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $301,500
- **Award type:** 3
- **Project period:** 2024-06-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11010550

## Citation

> US National Institutes of Health, RePORTER application 11010550, Genomic and functional approaches to characterize Chr1q gains in cancer (3R01CA276666-02S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11010550. Licensed CC0.

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