Both children and adults can develop cancer, but are pediatric cancers different than adult ones? A new study has found that, at least for melanoma, the two are fairly alike. It appears as though skin cancer in kids and skin cancer in adults have many similarities, which could help in treating this deadly condition.
Pediatric melanoma, though rare, is the most common type of skin cancer in children and adolescents. According to the National Cancer Institute, about 425 cases of melanoma are diagnosed among U.S. youth aged 19 and younger each year, and in recent decades, the prevalence of melanoma among adolescents aged 15 to 19 has increased annually by about two percent between 1973 and 2009. Fortunately, for 75 percent of pediatric patients in whom melanoma is diagnosed before spreading, long-term survival rates are now over 90 percent.
To further aid in the development of more efficacious diagnostic and therapeutic methods, researchers of the St. Jude Children’s Research Hospital — Washington University Pediatric Cancer Genome Project have recently undertaken the most extensive investigation to the researchers’ knowledge, of the genetic mutations that induce pediatric melanoma.
Their research, featured in the March issue of the Journal of Investigational Dermatology, sought to reveal the genetic basis of the three subtypes of pediatric melanoma.
Among the 23 pediatric melanoma patients in the study, whose ages ranged from nine months to 19 years old, 15 were diagnosed with conventional melanoma, three with melanoma developed from congenital melanocytic nevi (CMN) and five with spitzoid melanoma. Melanoma, a skin cancer which forms from melanin-producing cells, has variants such as congenital melanocytic nevi and spitz nevi that arise from different types of skin lesions.
Most scientists think that melanoma is a product of cumulative malignant results from multiple mutations, including oncogenic mutations in genes, such as the ones called BRAF (a gene that makes the protein B-Raf) and NRAS (the gene that makes the protein N-Ras). Utilizing whole genome sequencing and other techniques to determine genetic alterations, the researchers analyzed gene sequences for BRAF, NRAS and TERT promoter genes in all 23 pediatric melanoma cases. The TERT promoter gene helps make an enzyme called telomerase.
In the 15 cases of pediatric conventional melanoma, the study of single nucleotide variations revealed that over 80 percent of somatic mutations or acquired mutations comprised of cytidine tranforming to thymidine and guanine to adenine, changes indicative of the effect of UV light on the genome.
Thus, children and adolescents as well as adults are more prone to acquire melanoma following significant UV exposure. Moreover, the genomic sequences of pediatric conventional melanoma patients contained multiple copy number variations in regions similar to the areas observed in adult melanoma, further indicating that conventional melanoma is the same disease in children and adults.
Of the 15 conventional melanoma cases, 13 showed BRAF mutation. Mutations of the TERT promoter gene were also frequent. Another gene that exhibited alterations was the PTEN tumor suppressor gene, a gene that codes for a protein that helps suppress tumors, which showed variations either at its structural or nucleotide level. By contrast, the three pediatric patients diagnosed with CMN did not display alterations of the PTEN tumor suppressor gene, while they demonstrated oncogenic mutations of the NRAS gene.
Different from both conventional melanoma and CMN, the five spitzoid melanoma cases lacked BRAF and NRAS activating point mutations. It was noted that one of the five pediatric spitzoid melanoma patients who suffered from widespread disease was also the only one whose genome exhibited a TERT promoter mutation, identical to the alteration observed in conventional melanoma. The possibility of utilizing TERT promoter mutations as a likely sign of aggressive spitzoid melanoma is to be further investigated by the researchers.
By examining the genetic basis of the three subtypes of pediatric melanoma, the research group has illustrated that with regard to conventional melanoma, there are definite genomic similarities between pediatric and adult cases, suggesting that children and adolescents would benefit from therapy currently reserved for adults. Children and adolescents, the researchers urge, should also be able to participate in trials that test promising therapeutic agents.
As for prevention methods, the researchers recommend habitual sun protection from early on in life, although environmental factors affecting the likelihood of pediatric melanoma could not be fully explored in this study. The further understanding of prevention methods, as well as the refinement of diagnostic procedures, necessitates more comprehensive investigations into the genomic alterations underlying pediatric melanoma.
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