# Single cell analysis of the evolving mutational landscape in carcinogen exposed skin

> **NIH NIH R50** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2023 · $101,243

## Abstract

Abstract
The development of early detection approaches is fundamental to reduce the growing cancer
burden. Cellular accumulation of genetic mutations is believed to be the foundation of tumor
development, however, there is a fundamental lack of knowledge regarding the earliest stages of
tumorigenesis and whether certain cell populations may be more predisposed to acquire initial
driving mutations. Stem cells are long-lived cells which reside in tissues and serve as a
regenerative pool that actively maintain normal homeostasis and can repair tissue after injury.
Accumulating evidence indicates that stem cells may also serve as the cells of origin for
tumorigenesis in certain tissues and generate clonal expansions of mutated cells which could be
more susceptible to further genetic insults over time. As it is not feasible to address the evolving
mutational burden of stem cells in tissues of human individuals, this study will exploit mouse dorsal
skin, a highly informative regenerative model system with well characterized and distinct stem cell
populations. The dynamic mutation co-occurrence profiles of specific skin mouse stem cell
populations will be determined following exposure to known carcinogens utilizing a customizable,
single cell DNA-sequencing platform. This approach will identify whether certain mutational
profiles are selectively enriched and tolerated in specific stem cell populations over long periods
of time in functionally normal tissue following carcinogen exposure. The approach used by this
study could easily be adapted to screen many different chemical exposures and has the potential
to detect the earliest signs of cancer in similar epithelial tissue systems with shared stem cell
populations such as the lung and intestine – which are often exposed to long term environmental
and chemical insult - before tumors are evident and determine distinct carcinogen-exposure
signatures in cells.

## Key facts

- **NIH application ID:** 10674848
- **Project number:** 5R50CA251479-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Eve Kandyba
- **Activity code:** R50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $101,243
- **Award type:** 5
- **Project period:** 2020-08-11 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10674848

## Citation

> US National Institutes of Health, RePORTER application 10674848, Single cell analysis of the evolving mutational landscape in carcinogen exposed skin (5R50CA251479-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10674848. Licensed CC0.

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