More than one disease
Thanks to efforts like the St. Jude-Washington University Pediatric Cancer Genome Project, scientists have learned that childhood melanoma is not one disease, but multiple diseases. These subgroups include:
Conventional Melanoma: Melanocytic lesions with features similar to adult melanoma that occur almost exclusively in adolescents. These tumors often have BRAF and TERT promoter mutations.Spitz Melanoma and Atypical Spitz Tumors: Occur in younger patients and are characterized by copy number changes. These tumors typically have kinase fusions involving MAP3K8, NTRK, ALK, ROS1, RET, BRAF or MET.Giant congenital nevus melanomas: aggressive tumors with NRAS mutations and upregulation of TERT.
There are no reliable clinical or morphological features that can accurately predict the clinical behavior of childhood melanoma tumors. However, the registry offers the opportunity to better understand and potentially treat the natural history of these tumors.
“What we see from the registry data is that these are incredibly diverse tumors. Some patients need drastic measures. For many others, masterful viewing is the best option,” said last author Armita Bahrami, MD, formerly of St. Jude and now Emory University: “It is critical for the healthcare team to consider all available clinical, pathological and genomic data to assign patients to the appropriate risk category.”
The registry has been open and registering patients since 2016. The researchers analyzed data from the first 70 patients who participated and categorized them as one of three recognized subgroups, or as “other.” From the registry, the researchers were able to determine that most spitzoid melanomas have a gene fusion, usually with MAP3K8. They also found that spitzoid melanomas that do not have a TERT mutation have a benign clinical course.
For conventional melanoma, the researchers found that the most common mutation was in the BRAF gene. Conventional melanoma patients with advanced disease did not fare as well as those diagnosed with early-stage disease. The study also showed that giant congenital nevus melanomas all had NRAS mutations and all patients died from their disease.
A focus on rare diseases
These results emphasize the need to consider patient age, pathology assessment, and integrated genomic analysis, not only to arrive at the correct diagnosis, but also to anticipate the clinical behavior of these tumors.
“Now that we have all this information available, we can be significantly more selective and integrate this information into treatment decision-making,” Pappo said. “It will help us provide the best possible information for the patient regarding prognosis, recurrence and the need for additional surgery or therapy.”
A majority of the patients on the registry were treated in St. Jude through a special pediatric melanoma clinic. The clinic is ongoing and held virtually during the COVID-19 pandemic.
The other authors of the study are Teresa Wright, University of Tennessee Health Science Center, and Valerie McPherson, Haitao Pan, Fang Wang, Lu Wang, Margaret Hussong, Dana Hawkins, Sue Caste and Andrew Davidoff, all of St. Jude.
The study was funded by the National Institutes of Health (P30CA021765) and ALSAC, the St. Jude fundraising and awareness organization.
St. Jude Children’s Research Hospital
St. Jude Children’s Research Hospital is a leader in how the world understands, treats and cures childhood cancer and other life-threatening diseases. It is the only National Cancer Institute-designated Comprehensive Cancer Center dedicated solely to children. Treatments developed in St. Jude have helped increase childhood cancer survival rates from 20% to 80% since the hospital opened more than 50 years ago. St. Jude freely shares the breakthroughs it makes, and every child saved in St. Jude means doctors and scientists around the world can use that knowledge to save thousands more children. Families never receive a bill from St. Jude for treatment, travel, housing and food – because the whole family should be concerned about helping their child. For more information, visit stjude.org or follow St. Jude on social media at @stjuderesearch.