Project description:The goal of this study was to profile the transcriptome of different small round cell sarcomas from patient-derived xenografts. We derive unique gene expression associated with each of the fusion proteins driving these sarcomas.
Project description:To conduct exome and transcriptome profiling to identify secondary recurrent mutations, multi-site phylogenetic analyse and immune characterization of Desmoplastic Small Round Cell Sarcoma.
| EGAS00001004575 | EGA
Project description:RNAseq of undifferentiated small round cell sarcomas
Project description:We investigated the gene expression changes in a library of small cell lung carcinoma (SCLC) patient-derived xenograft (PDX) models.
Project description:Small RNAs in FACS-purified spermatogonia, spermatocytes (L/Z and P/D) and round spermatids were sequenced to study piRNA populations.
Project description:Desmoplastic small round cell tumor (DSRCT) is a rare and incurable malignancy characterized by the oncogenic EWSR1-WT1 transcription factor. This study exploited a novel DSRCT patient-derived xenograft (PDX), which reproduces histomorphological and molecular characteristics of the paired clinical tumor, to comparatively assess the activity of cytotoxic and targeted anticancer agents. Anti-tumor effect was moderate for single-agent doxorubicin, pazopanib and larotrectenib [maximum tumor volume inhibition (max TVI): 55-66%] while trabectedin had a higher effect (max TVI: 82%). Single-agent vinorelbine, irinotecan and eribulin achieved a nearly complete tumor growth inhibition (max TVI: 96-98%), although tumors started to re-growth after the end of treatment. Combination of irinotecan with either eribulin or trabectedin resulted in complete responses which were maintained until the end of the experiment for irinotecan plus trabectedin. Irinotecan-based combinations almost completely abrogated the expression of proteins involved in the G2/M checkpoint preventing cell entrance in mitosis and induced apoptotic and necroptotic cell death. This study emphasizes the importance of patient-derived pre-clinical models to explore new treatments in DSRCT and fosters clinical investigation in the activity of irinotecan plus trabectedin.
Project description:The tumor microenvironment plays a crucial role in soft tissue sarcoma development and response to therapy. We used single cell RNA sequencing to analyze the malignant, immune, and other stromal cells present within soft tissue sarcomas.