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View article: Fancl-mutant mice reveal central role of monoubiquitination in Fanconi anemia and a model for therapeutic gene editing
Fancl-mutant mice reveal central role of monoubiquitination in Fanconi anemia and a model for therapeutic gene editing Open
Fanconi anemia (FA) is a rare genetic disorder causing progressive loss of hematopoietic stem cells (HSCs) and bone marrow failure. Most cases result from deficient monoubiquitination of FANCD2 by the FA core complex. However, as additiona…
View article: EXTH-93. Combination of ALK2 and cholesterol targeting agents exploits linked genetic and metabolic dependencies in diffuse midline glioma
EXTH-93. Combination of ALK2 and cholesterol targeting agents exploits linked genetic and metabolic dependencies in diffuse midline glioma Open
The discovery that ACVR1-mutations arise in ~25% of DMG H3K27-altered patients has led assessment of both the dependency of ACVR1-mutant cells on ALK2 and the effectiveness of ALK2 inhibitors (ALK2i), however as single-agents these are yet…
View article: Multidimensional, integrative profiling identifies BCL2L1 methylation as a predictor of MCL1 dependency in pediatric malignancies
Multidimensional, integrative profiling identifies BCL2L1 methylation as a predictor of MCL1 dependency in pediatric malignancies Open
Pediatric high-grade gliomas (pHGGs) are the most aggressive brain tumors in children, necessitating innovative therapies to improve outcomes. Unlike adult gliomas, recent research reveals that childhood gliomas have distinct biological fe…
View article: Emerging and Biological Concepts in Pediatric High-Grade Gliomas
Emerging and Biological Concepts in Pediatric High-Grade Gliomas Open
Primary central nervous system tumors are the most frequent solid tumors in children, accounting for over 40% of all childhood brain tumor deaths, specifically high-grade gliomas. Compared with pediatric low-grade gliomas (pLGGs), pediatri…
View article: HGG-23. MAPPING GENETIC DEPENDENCIES IN PAEDIATRIC HIGH GRADE GLIOMAS AT GENOME-SCALE
HGG-23. MAPPING GENETIC DEPENDENCIES IN PAEDIATRIC HIGH GRADE GLIOMAS AT GENOME-SCALE Open
BACKGROUND Pediatric high-grade gliomas (HGGs) present a therapeutic challenge due to their aggressive behavior and limited treatment options. Traditional treatments often fall short in addressing the genetic complexity and aggressiveness …
View article: DIPG-22. A NOVEL ROLE FOR ACVR1/ALK2 IN REGULATING CHOLESTEROL BIOSYNTHESIS PROVIDES A NEW COMBINATORIAL THERAPEUTIC APPROACH FOR PATIENTS WITH DMG
DIPG-22. A NOVEL ROLE FOR ACVR1/ALK2 IN REGULATING CHOLESTEROL BIOSYNTHESIS PROVIDES A NEW COMBINATORIAL THERAPEUTIC APPROACH FOR PATIENTS WITH DMG Open
BACKGROUND The discovery of somatic mutations in ACVR1, which encodes the serine/threonine kinase ALK2, in 20-25% of diffuse midline glioma H3K27-altered (DMG-H3K27) patients has led to the development of numerous chemotypes of ALK2 inhibi…
View article: HGG-53. MULTI-DIMENSIONAL INTEGRATIVE PROFILING IDENTIFIES BCL2L1 METHYLATION AS A PREDICTIVE BIOMARKER FOR MCL-1 ACTIVITY IN PEDIATRIC HIGH-GRADE GLIOMAS
HGG-53. MULTI-DIMENSIONAL INTEGRATIVE PROFILING IDENTIFIES BCL2L1 METHYLATION AS A PREDICTIVE BIOMARKER FOR MCL-1 ACTIVITY IN PEDIATRIC HIGH-GRADE GLIOMAS Open
BACKGROUND Pediatric high-grade gliomas (pHGGs) pose a significant challenge as the most aggressive central nervous system tumors in children. The lack of effective treatment and poor survival rates emphasize the critical need for innovati…
View article: SYST-15 GENERATION AND MULTI-DIMENSIONAL PROFILING OF A CHILDHOOD CANCER CELL LINE ATLAS DEFINES NEW THERAPEUTIC OPPORTUNITIES
SYST-15 GENERATION AND MULTI-DIMENSIONAL PROFILING OF A CHILDHOOD CANCER CELL LINE ATLAS DEFINES NEW THERAPEUTIC OPPORTUNITIES Open
Paediatric solid tumours are the leading cause of cancer related death amongst children. Identification of paediatric-specific targeted therapies necessitates the use of paediatric cancer models that faithfully recapitulate the patient’s d…
View article: Fancm has dual roles in the limiting of meiotic crossovers and germ cell maintenance in mammals
Fancm has dual roles in the limiting of meiotic crossovers and germ cell maintenance in mammals Open
Meiotic crossovers are required for accurate chromosome segregation and producing new allelic combinations. Meiotic crossover numbers are tightly regulated within a narrow range, despite an excess of initiating DNA double-strand breaks. He…
View article: Generation and multi-dimensional profiling of a childhood cancer cell line atlas defines new therapeutic opportunities
Generation and multi-dimensional profiling of a childhood cancer cell line atlas defines new therapeutic opportunities Open
View article: The Interleukin-11/IL-11 Receptor Promotes Glioblastoma Survival and Invasion under Glucose-Starved Conditions through Enhanced Glutaminolysis
The Interleukin-11/IL-11 Receptor Promotes Glioblastoma Survival and Invasion under Glucose-Starved Conditions through Enhanced Glutaminolysis Open
Glioblastoma cells adapt to changes in glucose availability through metabolic plasticity allowing for cell survival and continued progression in low-glucose concentrations. However, the regulatory cytokine networks that govern the ability …
View article: SSNIP-seq: A simple and rapid method for isolation of single-sperm nucleic acid for high-throughput sequencing
SSNIP-seq: A simple and rapid method for isolation of single-sperm nucleic acid for high-throughput sequencing Open
We developed a simple and reliable method for the isolation of haploid nuclei from fresh and frozen testes. The described protocol uses readily available reagents in combination with flow cytometry to separate haploid and diploid nuclei. T…
View article: sgcocaller and comapr: personalised haplotype assembly and comparative crossover map analysis using single-gamete sequencing data
sgcocaller and comapr: personalised haplotype assembly and comparative crossover map analysis using single-gamete sequencing data Open
Profiling gametes of an individual enables the construction of personalised haplotypes and meiotic crossover landscapes, now achievable at larger scale than ever through the availability of high-throughput single-cell sequencing technologi…
View article: <i>synapsis</i>: A Bioconductor package to automate the analysis of meiotic double-strand break repair and crossover formation
<i>synapsis</i>: A Bioconductor package to automate the analysis of meiotic double-strand break repair and crossover formation Open
Summary Immunofluorescent staining is commonly used to generate images to characterise cytological phenotypes. The manual quantification of DNA double-strand breaks and their repair intermediates during meiosis using image data requires a …
View article: <i>Fancm</i> regulates meiotic double-strand break repair pathway choice in mammals
<i>Fancm</i> regulates meiotic double-strand break repair pathway choice in mammals Open
Meiotic crossovers are required for accurate chromosome segregation and to produce new allelic combinations. Meiotic crossover numbers are tightly regulated within a narrow range, despite an excess of initiating DNA double-strand breaks. H…
View article: sgcocaller and comapr: personalised haplotype assembly and comparative crossover map analysis using single-gamete sequencing data
sgcocaller and comapr: personalised haplotype assembly and comparative crossover map analysis using single-gamete sequencing data Open
Profiling gametes of an individual enables the construction of personalised haplotypes and meiotic crossover landscapes, now achievable at larger scale than ever through the availability of high-throughput single-cell sequencing technologi…
View article: Personalized genome structure via single gamete sequencing
Personalized genome structure via single gamete sequencing Open
Genetic maps have been fundamental to building our understanding of disease genetics and evolutionary processes. The gametes of an individual contain all of the information required to perform a de novo chromosome-scale assembly of an indi…
View article: The role of interleukin‑6‑STAT3 signalling in glioblastoma (Review)
The role of interleukin‑6‑STAT3 signalling in glioblastoma (Review) Open
Glioblastoma is the most common type of malignant brain tumor among adults and is currently a non-curable disease due primarily to its highly invasive phenotype, and the lack of successful current therapies. Despite surgical resection and …