Genetic landscape of indolent and aggressive Kaposi sarcomas

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. We compared genetic landscape including tumor mutational burden between the two forms of indolent and agressive KS. Methods We performed whole-exome sequencing on a cohort of 21 KS patients. We compared tumour mutational burden (TMB) between the two forms of KS and between KS tumours and tumours or other types. 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.

Automated summary

The study found that aggressive Kaposi sarcoma (KS) differs significantly from indolent KS in terms of tumor mutational burden, with aggressive KS having a higher burden and a larger number of mutations.