The scientists at St. Jude Children’s Research Hospital created a registry called Molecular Analysis of Childhood MELanocytic Tumors (MACMEL) to better understand pediatric melanoma.1
“What’s different about the MACMEL registry is that it’s prospective,” said corresponding author Alberto Pappo, MD, St. Jude Solid Tumor Division Director, Memphis, Tennessee, in a press release announcing the registry’s creation. . “We see the vast majority of patients enrolled as part of the melanoma clinic in St. Jude. We can monitor these patients and perform detailed pathology and molecular analyses.”
The scientists who worked on Washington University’s Pediatric Cancer Genome Project found that childhood melanoma is multiple diseases rather than one. Those diseases are:
Conventional Melanoma: Melanocytic lesions with features similar to adult melanoma occur almost exclusively in adolescents. These tumors often have proto-oncogenic B-Raf (BRAF) and telomerase reverse transcriptase (TERT) promoter mutations.1 Spitz melanoma and atypical spitz tumors: These occur in younger patients and are characterized by changes in copy number. These tumors typically have kinase fusions in which mitogen-activated protein kinase kinase kinase 8 (MAP3K8), neurotrophic tyrosine receptor kinase (NTRK), anaplastic lymphoma receptor tyrosine kinase (ALK), ROS proto-oncogene 1, receptor tyrosine kinase (ROS1), rearranged during transfection (RET), BRAF- or -proto-oncogene and receptor tyrosine kinase (MET).1 Giant congenital nevus melanomas: these are aggressive tumors with NRAS proto-oncogene, GTPase (NRAS) mutations and upregulation of TERT.1
As of now, the clinical behavior of childhood melanoma tumors cannot be accurately predicted by clinical or morphological features, but the registry offers an opportunity to better understand and potentially treat them, according to the release.
“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 a professor at Emory University, Atlanta, Georgia, said in the release, “It is critical for the healthcare team to consider all available clinical, pathological and genomic data to assign patients to the appropriate risk category.”
Since 2016, the registry has been registering patients and researchers have analyzed the data of the first 70 patients and classified them into the 3 subgroups above or as others. Using that data, it has been determined that most spitzoid melanomas have a gene fusion usually involving MAP3K8, and it was found that spitzoid melanomas that do not have a TERT mutation have a benign clinical course.
With regard to the conventional melanomas, the registry found that the most common mutation was in the BRAF gene and that patients diagnosed with advanced disease did not do as well as the earlier stage disease. The study also showed that the giant congenital nevus melanomas all have NRAS mutations and all diagnosed patients died as a result of the melanoma.
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 study was funded by the National Institutes of Health (P30CA021765) and American Lebanese Syrian Associated Charities (ALSAC), St. Jude’s fundraising and awareness-raising organization.
1. Melanoma registry results shed light on rare childhood cancers. St Jude Children’s Research Hospital. Press release. July 6, 2021. Accessed July 14, 2021. https://www.stjude.org/media-resources/news-releases/2021-medicine-science-news/melanoma-registry-results-shine-light-on-rare – pediatric-cancer.html