# Project 2: Primary melanoma DNA Methylation profiling for evaluating subtypes and survival

> **NIH NIH P01** · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · 2020 · $11,996

## Abstract

Although it has been established that melanomas frequently have aberrant DNA methylation patterns, it is
unknown if DNA methylation of primary melanoma defines biologically relevant subclasses or predicts diseasespecific
survival. This project’s goals are to identify and characterize DNA methylation-based primary
melanoma subclasses, and train, test, and validate a CpG signature prognostic for disease-specific survival in
primary melanoma. Our hypothesis is that DNA methylation in primary melanoma will define subgroups
(including a poor-prognostic CIMP - ‘CpG island methylator phenotype’ subtype) and that a CpG signature will
be prognostic for melanoma survival. Illumina Infinium MethylationEPIC (850K) array profiling will be performed
on the same 1,000 primary melanomas to be utilized throughout this program project. These melanomas will
be from AJCC stage IIA/IIB/IIC/IIIA/IIIB patients, including 500 from patients who died due to melanoma within
5 years and 500 from those who lived at least 5 years matched on stage. In Aim 1, using data from the 1,000
primary melanomas, we will identify methylation-based melanoma subclasses, characterized by 5-year survival
and other outcomes, demographic factors, centrally reviewed histopathological features, a CD3/CD8/FOXP3
immune profile, PD1 and PDL1 protein expression, somatic mutations, copy number alterations, and mRNA
and miRNA expression data. Further characterization will determine if the subclasses are associated with
biologically relevant DNA methylation signatures that our group and others have previously produced from
independent datasets. In Aim 2 using statistical modeling, we will train a primary melanoma CpG signature
prognostic for death from melanoma within 5 years (the primary outcome) using 660 of the primary melanomas
and test it using 340 of the primary melanomas. We will determine whether this CpG survival signature adds
information to AJCC staging. As secondary outcomes, we will also develop signatures for recurrence within 5
years, sentinel lymph node (SLN) positivity, and distant recurrence after negative SLN biopsy. In Aim 3, we will
technically validate DNA methylation levels of CpGs/genes in the survival signature using quantitative
methylation-specific polymerase chain reaction (PCR). For select markers, we will quantitatively measure their
protein expression differences using multiplexed immunohistochemistry, comparing primary melanomas from
patients alive and those who died within 5 years of diagnosis and assess the function of the most prognostic
targets in Project 3. Our goal is to identify and characterize DNA methylation-based primary melanoma
subclasses and discover and validate a CpG signature prognostic for survival from melanoma that adds
information to AJCC staging. We will initiate application of the signature to a clinically viable assay prognostic
for survival. This project should allow identification of melanoma patients expected to have worse survival and
who coul...

## Key facts

- **NIH application ID:** 10268363
- **Project number:** 3P01CA206980-04S1
- **Recipient organization:** UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
- **Principal Investigator:** NANCY E. THOMAS
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $11,996
- **Award type:** 3
- **Project period:** 2017-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10268363

## Citation

> US National Institutes of Health, RePORTER application 10268363, Project 2: Primary melanoma DNA Methylation profiling for evaluating subtypes and survival (3P01CA206980-04S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10268363. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*