# Molecular basis of melanocytic nevi

> **NIH NIH K23** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2021 · $167,940

## Abstract

Melanocytic nevi (moles) are exceedingly common and commonly biopsied benign melanocytic neoplasms that
are mimics, risk factors, and potential precursors for melanoma, the deadliest of the common forms of skin
cancer. Melanocytic neoplasms comprise approximately 50% of all skin biopsies performed. If diagnosed early,
melanoma is curable. However, the diagnosis is currently based on histological examination and in up to 10-
25% of cases, pathologists do not agree on the diagnosis. Therefore, novel markers are needed that define both
benign and malignant melanocytic neoplasms and could be used for diagnosis and as therapeutic targets. While
extensive sequencing efforts have been conducted on melanoma, similar studies on nevi, especially common
acquired and dysplastic nevi, the most common pigmented lesions in clinical practice, are limited.
 The overall hypothesis is that melanocytic nevi show distinct genomic signatures different from
melanoma. Utilizing these data will ultimately lead to development of much needed novel objective diagnostic
strategies and identification of therapeutic targets.
 The first aim is to define the genomic landscape of sporadic melanocytic nevi, specifically common
acquired and dysplastic nevi. The hypothesis is that nevi show recurrent mutations in a limited number of key
genes indicating the existence of molecularly distinct nevus subtypes. Furthermore, the hypothesis is that the
genomic landscape correlates with histological features, the current basis for diagnosis of melanocytic tumors.
We will perform whole exome and genome sequencing to define main drivers, co-mutations, copy number
aberrations, and mutation signatures, and correlate these with detailed clinical and histological features.
 The second aim is to investigate how germline mutations influence the number and genomic landscape
of nevi. Specifically, we will examine a cohort of individuals with Cardio-Facio-Cutaneous syndrome and Costello
syndrome caused by germline mutations in various genes of the Ras pathway, the same genes that are critical
for melanomagenesis. The hypothesis is that certain germline Ras pathway mutations predispose to the
development of nevi but additional co-mutations are required for nevogenesis. We will determine the number of
nevi, the strongest risk marker of melanoma, as well as the dermoscopic pattern of nevi, a potential correlate of
the germline background. We will collect RASopathy nevi for whole exome and genome sequencing to define
genetic events of nevogenesis, including the role of the germline mutation in driving nevogenesis and the
presence of potential somatic co-mutations contributing to nevogenesis.
 By studying sporadic nevi and nevi arising in the setting of germline Ras pathway mutations we will define
the drivers and genomic landscape of nevi - the benign counterparts, mimics and potential precursors of
melanoma. Ultimately, these studies will lead to identification of much needed novel objective diagnostic
m...

## Key facts

- **NIH application ID:** 10214534
- **Project number:** 5K23AR074530-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Maija Helena Tuulia Kiuru
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $167,940
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10214534

## Citation

> US National Institutes of Health, RePORTER application 10214534, Molecular basis of melanocytic nevi (5K23AR074530-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10214534. Licensed CC0.

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