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Rhabdoid tumors (RT) are embryonal neoplasms occurring most frequently in the central nervous system where they are termed atypical teratoid rhabdoid tumor (ATRT). A common hallmark of RT is homozygous loss of the BAF complex subunit SMARCB1. RT patients have a poor prognosis with an overall survival time of 17 months and >60% of patients suffer from relapses. The lack of an optimal treatment strategy could be attributed to the heterogeneity within and between different subgroups of ATRT. Despite the recent advancements in characterizing RT at a molecular level, the cellular origin of RT remains elusive. Thus, this study focused on the identification of the cellular origin of MYC-RT and underlying epigenetic deregulations which account for the cellular heterogeneity in these tumors. We showed that Smarcb1 abrogation in Sox2-positive progenitor cells at E6.5 give rise to RT of the MYC and SHH subgroup in genetically engineered mouse models (GEMM). To uncover distinct cells of origin (COO) for the SHH and MYC subgroups, unbiased computational approaches were used to compare single-cell transcriptomes of GEMMs with single-cell reference maps of murine early embryogenesis. While SHH tumors arise from mid/hindbrain progenitor cells, primordial germ cells (PGCs) emerge as COO of both intracranial and extracranial MYC tumors. PGCs as COO of MYC-RT were validated in vivo by using PGC-specific Smarcb1 knockout mouse model. We further characterized a deregulated transcriptome in MYC-RT compared to PGCs, which is sustained by a subset of epigenetically driven tumor cells. Deregulated expression of genes driving methylation/demethylation processes in MYC tumors and regression of these tumors upon treatment with decitabine in vitro and in vivo, indicates that DNA methylation plays a key role in cellular transformation and development of MYC-RT.

L- asparaginase (EC 3.5.1.1) is an enzyme which converts L- asparagine to L-aspartic acid and ammonia; L- glutaminase (EC 3.5.1.2) is an enzyme which catalyzes the conversion of L-glutamine to L- glutamic acid and ammonia. Both of these enzymes have been used in as chemotherapeutic agents. Among different sources of L- asparaginase and L-glutaminase enzymes producers, microbial strains possess an elevated edge over other enzyme producers; these enzymes produced by different microbial strains differ in some physiological, biochemical, catalytic and immunological properties. This led to the continuous screening program for isolation of novel microbial strains that could produce an effective enzyme with few limitations at use. A bacterial strain isolated from soil and identified as Pseudomonas aeruginosa PAO1 had been found to be capable of producing both extracellular L- Asparaginase and L- Glutaminase enzymes. The enzymes were produced under solid state fermentation. Effects of different fermentation parameters for production of these enzymes were determined. Some physicochemical properties of both of these enzymes were determined. The results obtained in this study revealed the potential of Pseudomonas aeruginosa PAO1 as a source of both L-Asparaginase and L- Glutaminase enzymes, which have gained significance in pharmaceutical industry. The uses of inexpensive agro- industrial wastes in this study have important economic advantages over submerged fermentation.

L- asparaginase ( EC 3.5.1.1) is an enzyme which converts L- asparagine to L-aspartic acid and ammonia; L- glutaminase ( EC 3.5.1.2) is an enzyme which catalyzes the conversion of L-glutamine to L- glutamic acid and ammonia. Both of these enzymes have been used in as chemotherapeutic agents. Among different sources of L- asparaginase and Lglutaminase enzymes producers, microbial strains possess an elevated edge over other enzyme producers; these enzymes produced by different microbial strains differed in some physiological, biochemical, catalytic and immunological properties. This led to the continuous screening program for isolation of novel microbial strains that could produce an effective enzyme with few limitations at use. A bacterial strain isolated from soil and identified as Psedomonas aeruginosa had been found to be capable of producing both extracellular L- Asparaginase and L- Glutaminase enzymes. The enzymes were produced under solid state fermentation. Effects different fermentation parameters for production of these enzymes were determined. Some physicochemical properties of both of these enzymes were determined. The results obtained in this study revealed the potential of Pseudomonas aeruginosa as a source of both L-Asparaginase and L- Glutaminase enzymes, which have gained significance in pharmaceutical industry. The uses of inexpensive agro- industrial wastes in this study have important economic advantages over submerged fermentation.