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 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: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: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:This data was utilized to assess the utility of perfusion culture in cultivating spheroids of sarcoma cells. The differences between spheroids cultured with perfusion and without perfusion were analyzed through mass spectrometry. The spheroids were fabricated from NCC-UPS4-C1 cell line derived from a patient with undifferentiated pleomorphic sarcoma.
Project description:We used array-based comparative genomic hybridization to identify copy number alterations in the TP53 and RB1 tumor suppressor genes in 64 myxofibrosarcoma and 30 undifferentiated pleomorphic sarcoma primary untreated tumor samples, and found that 68% of tumor samples had shallow or deep deletions in one or both genes.
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.