Genetic landscape of indolent and aggressive Kaposi sarcomas

• Published in: Journal of the European Academy of Dermatology and Venereology 2022-12, Vol.36 (12), p.2343-2351
• Main Authors: Malouf, G.G., Lu, X., Mouawad, R., Spano, J.‐P., Grange, P., Yan, F., Aractingi, S., Su, X., Dupin, N.
• Format: Article
• Language: English
• Subjects: Acquired Immunodeficiency Syndrome; Genetics; Herpesvirus 8, Human - genetics; Humans; Life Sciences; Mutation; Sarcoma, Kaposi - pathology; Skin Neoplasms - genetics
• ISSN: 0926-9959; 1468-3083; 1468-3083
• DOI: 10.1111/jdv.18463

Background Kaposi sarcoma (KS) is a rare skin tumour caused by herpesvirus 8 infection and characterized by either indolence or an aggressive course necessitating systemic therapies. The genetic basis of this difference remains unknown. Objectives To explore the tumour mutational burden in indolent and aggressive KS. Methods We performed whole‐exome sequencing on a cohort of 21 KS patients. We compared genetic landscape including tumor mutational burden between the two forms of indolent and agressive KS. Results Aggressive KS tumours had a significantly higher TMB and a larger cumulative number of deleterious mutations than indolent KS tumours. In addition, all aggressive tumours had at least three deleterious mutations, whereas most indolent tumours harboured only one or no predicted deleterious mutations. Deleterious mutations listed in the Cancer Gene Census were detected exclusively in patients with aggressive disease. An analysis of somatic copy‐number alterations (SCNA) revealed a tendency towards higher number of alterations in aggressive KS. Conclusions These data suggest that SCNA alterations and an increase in mutational burden promote aggressive KS and that it might be more appropriate to consider indolent KS as an opportunistic skin disease rather than a cancer.