Project description:Analysis of undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma like tumors from BrafCa, p53Fl/Fl mouse model of soft tissue sarcoma
Project description:Analysis of undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma-like tumors from LSL-KrasG12D, p53Fl/Fl mouse model of soft tissue sarcoma.
Project description:20 tumor samples run in duplicates, consisting of pleomorphic sarcomas; classfied as leiomyosarcoma or high-grade undifferentiated pleomorphic sarcoma.
Project description:Analysis of undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma-like tumors from LSL-KrasG12D, p53Fl/Fl mouse model of soft tissue sarcoma. Murine soft tissue sarcomas (n = 17) were compared to normal muscle (n = 4). Tumors were isolated surgically from soft tissue sarcomas generated by conditional Kras and p53 alleles. Tumors were induced using an adenovirus expressing Cre recombinase. Normal muscle samples were isolated from mice of the same genotype without tumor induction.
Project description:Undifferentiated pleomorphic sarcoma (UPS) and related tumors are the most common type of soft tissue sarcoma. However, this spectrum of tumors has different etiologies with varying rates of metastasis and survival. Two dermal-based neoplasms in this class of pleomorphic sarcomas, atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS), are challenging to differentiate at initial biopsy but vary significantly in prognosis. We performed single-cell transcriptomics on five AFX and PDS biopsy specimens as well as both single-cell and spatial transcriptomics on one PDS excision specimen to better characterize these tumors. The top differential genes between AFX and PDS were predictive of overall survival in 17 other cancers included in the Human Protein Atlas. Of these genes, COL6A3 and BGN predicted overall survival and metastasis-free survival in independent cohorts of 46 and 38 UPS tumors, respectively. COL6A3 was most predictive of overall survival in UPS patients and outperformed an established sarcoma prognostic gene panel at predicting metastasis in UPS.
Project description:Undifferentiated pleomorphic sarcoma (UPS) and related tumors are the most common type of soft tissue sarcoma. However, this spectrum of tumors has different etiologies with varying rates of metastasis and survival. Two dermal-based neoplasms in this class of pleomorphic sarcomas, atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS), are challenging to differentiate at initial biopsy but vary significantly in prognosis. We performed single-cell transcriptomics on five AFX and PDS biopsy specimens as well as both single-cell and spatial transcriptomics on one PDS excision specimen to better characterize these tumors. The top differential genes between AFX and PDS were predictive of overall survival in 17 other cancers included in the Human Protein Atlas. Of these genes, COL6A3 and BGN predicted overall survival and metastasis-free survival in independent cohorts of 46 and 38 UPS tumors, respectively. COL6A3 was most predictive of overall survival in UPS patients and outperformed an established sarcoma prognostic gene panel at predicting metastasis in UPS.
Project description:In this work, we utilise sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) for proteomic profiling of formalin fixed paraffin embedded (FFPE) specimens from a cohort of STS patients (n=36) across four histological subtypes (leiomyosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma). We quantified 2951 proteins in all cases and show that there is a significant enrichment of gene sets associated with smooth muscle contraction in leiomyosarcoma, RNA splicing regulation in synovial sarcoma and leukocyte activation in undifferentiated pleomorphic sarcoma. We further identified a subgroup of STS cases (independent of histological subtype) that have a distinct expression profile in a panel of 133 proteins, with worse survival outcomes when compared to the rest of the cohort. Our study highlights the value of comprehensive proteomic characterisation as a means to identify histotype-specific STS profiles that describe key biological pathways of clinical and therapeutic relevance; as well as for discovering new prognostic biomarkers in this group of rare and difficult-to-treat diseases.
Project description:High-grade complex karyotype sarcomas are a heterogeneous group of more than seventy tumors that vary in histology, clinical course, and patient demographics. Despite these differences, these high-grade sarcomas are treated similarly with varying outcomes. Pre-clinical models of distinct human sarcoma subtypes would advance insights into the relationships between sarcomas and inform therapeutic decisions. We describe the transformation of human mesenchymal stem cells into multiple subtypes of high-grade sarcoma. Using a pooled genetic screening approach, we identified key drivers and potential modifiers of transformation. YAP1, KRAS, CDK4, and PIK3CA were validated as drivers of four distinct sarcoma subtypes, undifferentiated pleomorphic sarcoma (UPS), myxofibrosarcoma (MFS), leiomyosarcoma (LMS), and osteosarcoma (OS). Histologically and phenotypically these tumors reflect human sarcomas including the pathognomonic complex karyotype and YAP1 amplification. Transcriptome analysis confirmed that these tumors accurately recapitulate human disease. This model is a tool that can be used to begin to understand pathways and mechanisms driving human sarcoma development, the relationship between sarcoma subtypes and to identify and test new therapeutic targets for this aggressive and heterogeneous disease.
2024-08-15 | GSE228213 | GEO
Project description:Primary pleomorphic undifferentiated sarcoma of genomic sequencing