Genetic Alterations Same in Adult and Pediatric Melanoma Patients

The St. Jude Children's Research Hospital--Washington University Pediatric Cancer Genome Project has found that melanoma in some adolescent and adult patients involves many of the same genetic alterations and would likely respond to the same therapy. The research appears in the March 2015 issue of the Journal of Investigational Dermatology.

The similarities involved adolescents with conventional melanoma tumors and included the first genetic evidence that sun damage contributes to melanoma in children and adolescents as well as adults. The findings stem from the most comprehensive analysis yet of the genetic alterations responsible for pediatric melanoma, which is the most common skin cancer in children and adolescents.

“This study shows that unlike many cancers, conventional melanoma is essentially the same disease in children and adults. That means we need to make it easier for adolescents to access promising therapeutic agents being tried in adults,” said co-corresponding author Alberto Pappo, MD, a member of the St. Jude Department of Oncology. “These results also underscore the importance of starting sun protection early and making it a habit for life.”

The researchers also identified distinct genetic alterations associated with other pediatric melanoma subtypes, including those associated with large congenital nevi (CNM) and spitzoid tumors. The alterations include a mutation that might help identify spitzoid patients who would benefit from aggressive therapy as well as those who could be cured with less intensive treatment.

This study included 23 melanoma patients ranging in age from 9 months to 19 years old. Researchers used whole genome sequencing and other techniques to compare the normal and tumor genomes of patients with three different types of melanoma for clues about the genetic alterations that underlie their disease.

The group included 15 patients with conventional melanoma. Unlike many pediatric cancers, their tumors included numerous genetic alterations, more than any of the childhood cancers studied so far by the Pediatric Cancer Genome Project. More than 90% of the tumors had genetic changes consistent with damage caused by ultraviolet light. More than 60% of the tumors had mutations in the BRAF oncogene, the PTEN tumor suppressor gene or the promoter region of a gene called TERT. The same alterations are found in melanoma in adults and promoted the unchecked cell division and other changes that are hallmarks of cancer.

In contrast to conventional melanoma, the three patients with the CNM subtype had mutations in the NRAS oncogene and no defects in PTEN. The patients all died of their disease.

In comparison, cancer caused the death of just one of the five spitzoid melanoma patients studied. That patient was also the only one with widespread disease and the only one whose tumor had a TERT promoter mutation. The finding has led to a larger study to determine if TERT promoter mutations can serve as a marker for spitzoid tumors that are destined to become clinically aggressive. The results are expected soon.

More in News