Paediatric melanoma

Oncology

Research

Disseminated melanoma has no effective treatment as chemotherapy and radiotherapy are not good options for this type of skin cancer. The molecular characterization of this cancer and its particularity in children is of special interest to develop effective therapies. It has been shown that most paediatric melanomas harbour alterations in CDKN2A and c-Kit genes20. CDKN2A gene is mutated in 5% of childhood melanomas21–23. The role of this important molecule is to check and inhibit when the cell is dividing without control. In patients where this is mutated, checking for the correct replication of the cell is not performed and mutations are introduced easier. Also, conventional melanomas in children have been found to carry a mutation in the TERT promoter (TERT-p) whereas melanomas arising in congenital nevi contained an activating NRASQ61 mutation and Spitzoid melanomas were characterized by chromosomal rearrangements resulting in activated kinase signalling (GSN/NTRK1 fusion)24.

Another commonly identified mutation of these tumours is a change from the valine (V) in position 600 of the BRAF protein to glutamic acid (E). This is commonly written BRAF V600E and also you can find it written BRAF c.1799T>A, indicating that the thymine in position 1799 of the cDNA that encodes this gene has mutated to alanine. This is a common aggressive mutation in some tumours and much research is being developed to block the consequences of it. One of the BRAF inhibitors tested in adult clinical trials is vemurafenib already in clinical use.

Other therapies being investigated are immune checkpoint inhibitors (ipilimumab and nivolumab) and inhibitors of mitogen-activated protein kinase/extracellular signal-regulated kinase (trametinib), which have all been licensed for metastatic melanoma in adults and have been included in trials in the adjuvant setting25. All of them are related to potential substantial toxicity and have not received approval for the paediatric population. However, the inclusion of children with metastatic melanoma in clinical trials deserves consideration, given that metastatic disease is not curable26 and the behaviour has been shown to be similar.


20Daniotti, M. et al. Cutaneous Melanoma in Childhood and Adolescence Shows Frequent Loss of INK4A and Gain of KIT. J. Invest. Dermatol. 129, 1759–1768 (2009).
21Mitkov, M. et al. Pediatric melanomas often mimic benign skin lesions: A retrospective study. J. Am. Acad. Dermatol. 75, 706–711.e4 (2016).
22Paradela, S., Fonseca, E. & Prieto, V. G. Melanoma in children. Arch. Pathol. Lab. Med. 135, 307–16 (2011).
23Wood, B. A. Paediatric melanoma. Pathology 48, 155–165 (2016).
24Lu, C. et al. The Genomic Landscape of Childhood and Adolescent Melanoma. J. Invest. Dermatol. 135, 816–823 (2015).
25Navid, F. et al. Feasibility of Pegylated Interferon in Children and Young Adults With Resected High-Risk Melanoma. Pediatr. Blood Cancer 63, 1207–1213 (2016).
26Merchant, M. S. et al. Phase I Clinical Trial of Ipilimumab in Pediatric Patients with Advanced Solid Tumors. Clin. Cancer Res. 22, 1364–1370 (2016).
Last modified
03 December 2019