Unveiling the Genetic Landscape of Pediatric Melanomas and Precursors

Melanoma is a dangerous and potentially life-threatening skin cancer. While it is rare in children, pediatric melanoma often behaves very differently than adult melanoma, making it more difficult to recognize, diagnose, and treat. Certain types of melanomas are more common in children, particularly those that arise from congenital melanocytic nevi (moles present at birth) and Spitzoid tumors, which can appear benign but may, in rare cases, present as melanoma. Because the precursor lesions (spitzoid lesions or congenital nevi) often look non-threatening, the standard medical approach has been to monitor them over time rather than remove them or conduct advanced genetic testing. This proposal was inspired by one of my own patients—a child who had a mole biopsied at age four. Fortunately, the pathology was considered benign at the time, and no genetic testing was performed, which is in line with standard care. The mole was watched for years without significant change, but during puberty, it suddenly became ulcerated. When it was removed, it was diagnosed as melanoma. Genetic testing revealed serious mutations, and unfortunately, the disease progressed rapidly. Had we known earlier what was happening at the molecular level, it’s possible that a more proactive treatment plan could have been offered—one that might have changed the outcome. Today, genetic testing is typically only done for melanomas. As a result, we know little about the precursor lesions which may have early molecular changes or otherwise signal a higher risk for progression. This project aims to bridge that gap by studying preserved tumor tissue from pediatric patients who had congenital nevi, spitzoid lesions, or melanomas biopsied in the past—which were never genetically analyzed. Using advanced sequencing technologies, we will look for hidden genetic changes that could help distinguish between harmless and high-risk tumors. Our study will examine archived cases of pediatric melanoma that were never tested using modern genomic tools. We will also study Spitzoid tumors, which are often difficult to classify, to better understand whether certain genetic signatures are associated with more aggressive behavior or have recognized genetic patterns. Finally, we will analyze congenital moles to see whether some of them carry genetic markers that could guide future care, including earlier intervention or targeted therapies that are already showing promise in related conditions. By combining decades of carefully collected tissue samples with modern genetic techniques, this research seeks to change how we understand and manage pediatric melanocytic tumors. Rather than relying solely on how a tumor looks under the microscope, we hope to identify genetic information that can help doctors make more informed decisions—leading to earlier diagnoses, better treatments, and improved outcomes for children at risk of melanoma.