Viral and Genetic Drivers of Growth and Metastasis of Anaplastic Kaposi Sarcoma in People Living with HIV

Division Of Basic Sciences - Nci

Investigators

Abstract

We have performed spatial transcriptome profiling of 16 samples to examine conventional and anaplastic KS tumors from patients and their matched KS PDX tumors, at multiple passages and at different sites of metastases. This will be complemented by bulk RNA sequencing. A bioinformatic pipeline is in place to define the transcriptional states and altered host networks that we expect will aid in our identification of novel therapeutic targets. We are analyzing for genomic instability in the aggressive anaplastic KS variants by targeted viral sequencing and whole exome sequencing. Large truncations in the KSHV genome have been mapped in two anaplastic KS and KS-PDX tumors thus far. Multiple candidate pathogenic host mutations have been identified that we are validating by orthogonal approaches. The response of anaplastic KS-PDX to liposomal doxorubicin, the front-line therapy, is being examined in mice by analyzing tumor growth and metastases.