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Science Papers Present Histone Modification Profiling Approach, Functional Analysis of Cancer Fusion Genes

A method for spatially resolved genome-wide profiling of histone modifications is described in Science this week. Called spatial-CUT&Tag, the technique combines cleavage under targets and tagmentation (CUT&Tag) chemistry, microfluidic deterministic barcoding, and next-generation sequencing. Its developers at Yale University demonstrate the approach in mouse embryos, revealing tissue-type-specific epigenetic regulations in concordance with ENCODE references and providing spatial information at tissue scale. "Spatial chromatin modification profiling in tissue may offer new opportunities to study epigenetic regulation, cell function, and fate decision in normal physiology and pathogenesis," the researchers write.

An efficient functional genomics approach to characterize the cellular consequences of gene fusions in cancer is reported in Science Advances this week. Fusion genes have been identified as drivers of tumorigenesis and promotors of tumor progression and represent target molecules with tremendous diagnostic and therapeutic potential. However, the functional impact and clinical relevance of cancer fusion genes remain poorly understood. To investigate, a multi-institute team led by scientists from the University of Texas MD Anderson Cancer Center developed a method consisting of efficient fusion reconstruction and sensitive cell viability and drug response assays, which they use to characterize around 100 fusion genes detected in patient samples of The Cancer Genome Atlas. Among their findings are a number of fusions involved in drug sensitivity and tumor growth. The investigators also offer an integrated, level-of-evidence classification system to prioritize gene fusions systematically. "Our approach demonstrates a potential way to fill the gap between sequencing-based fusion detection and target-based clinical actions," they write.

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