UV-induced mutations factor in pediatric melanoma

April 9, 2015

Clues about genetic alterations that underlie their disease.

The UV-induced mutational spectrum in pediatric conventional melanoma is similar to that in adults, suggesting the need for early sun protection and better access for pediatric patients to adult therapies, according to a new study.

In what researchers say is the most comprehensive genomic analysis of pediatric melanoma to date, they found unique genomic features for three pediatric melanoma subtypes. They also found that pediatric conventional melanomas contain a high burden of somatic single-nucleotide variations. Basically, the study shows that, unlike many cancers, conventional melanoma is essentially the same disease in children and adults, study author and St. Jude Children’s Research Hospital oncologist Alberto Pappo, M.D., said in a hospital press release.

The study, by the St. Jude Children’s Research Hospital-Washington University Pediatric Cancer Genome Project, is published in the March 2015 Journal of Investigational Dermatology. The study includes 23 melanoma pediatric patients, from nine months to 19 years old. Using whole-genome sequencing and other techniques, the researchers looked for clues about genetic alterations that underlie their disease.

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Among the 15 patients with conventional melanoma, more than 90% of the tumors had genetic changes consistent with UV-caused damage. 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.

Researchers also identified distinct genetic alterations associated with other pediatric melanoma subtypes, including those associated with large congenital nevi and spitzoid tumors. In contrast to conventional melanoma, the three patients with the congenital nevi subtype had mutations in the NRAS oncogene and no defects in PTEN. All three of those patients died a result of the disease.

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However, only one of the five patients with spitzoid melanoma died from the disease. That patient was also the only one with widespread disease and a TERT promoter mutation. Researchers are conducting a larger study to determine if TERT promoter mutations are a marker for clinically aggressive spitzoid tumors.

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“This is an important article for dermatologists,” Kathryn Schwarzenberger, M.D., dermatology chair and professor, University of Tennessee Health Science Center, wrote in an email to Dermatology Times. “We have long known that melanomas in children usually occur in one of three patterns:  conventional melanoma, those arising in congenital nevi, and spitzoid melanoma. This study looks at the genomic landscape of these different types of pediatric melanomas, revealing some fascinating findings.  First, conventional melanomas in children are genomically similar to those in adults.  This may allow children with these types of melanomas to benefit from many of the new therapeutic advances that we are now using on adults with melanoma. Another key finding is that the majority of conventional melanomas in these children showed evidence of genetic mutations that are consistent with damage from ultraviolet radiation. Finally, the study revealed genetic mutations that may help us better identify which spitzoid tumors have the potential to be aggressive.”

Dermatologists should educate patients that sun protection should start on day one of life, according to Dr. Shwarzenberger, who is not a study author.

“These findings will definitely strengthen the AAD's fight to protect youth from harm by indoor tanning,” she wrote. “I never wish to diagnose melanoma in a child, but I now feel more confident that we are getting a handle on this potentially devastating disease.”

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