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Pediatric Case of Spitzoid Melanoma: Focus on MAP3K8 Signaling Cascade

By: Alison Tewksbury
Posted: Wednesday, May 8, 2019

About half of the cases of spitzoid melanoma have unknown genetic drivers. To shed more light on this type of skin cancer, which is the most common pediatric melanoma, Scott Newman, PhD, of St. Jude Children’s Research Hospital, Memphis, and colleagues focused on an 11-year-old boy with a progressive case of spitzoid melanoma. Based on genome mapping, they identified a novel gene fusion of MAP3K8, which may prove to be a biomarker of response to treatment. Their results of this single-patient genome analysis were published in Nature Medicine.

Based on the results of their genetic analysis, the MEK inhibitor trametinib was initiated and resulted in a transient response in the young boy. Following this response, the genomes of 49 adolescent patients with spitzoid melanomas were assessed, and MAP3K8 fusions were found in 11 cases (22%). Researchers found a “pattern of mutual exclusivity between MAP3K8 rearrangements and other fusions…implying that MAP3K8 was the driver oncogene in these cases.” All tumors studied showed MEK1/2 phosphorylation.

According to the authors, MAP3K8 overexpression has been a “frequently mutated gene in cancer,” including breast, ovarian, and lung cancers as well as squamous cell carcinoma. “The substantial body of in vitro evidence suggests that removal of the final exon of MAP3K8 through fusion or truncation is an oncogenic event that can drive spitzoid and other melanomas,” they explained.

“This research suggests MAP3K8 should be incorporated into cancer genomic panels in the future,” stated coauthor Armita Bahrami, MD, of the St. Jude Department of Pathology, in an institutional press release. “These newly identified alterations, including gene fusions, have the potential to influence treatment,” added coauthor Jinghui Zhang, PhD, Chair of the St. Jude Computational Biology Department.

Disclosure: The study authors reported no conflicts of interest.



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