Publications by authors named "Megan L Insco"

The biological and clinical relevance of gene fusions in melanoma is unknown. Reports and preclinical data have suggested that tumor cells with specific rearrangements such as RAF1 gene fusions could be therapeutically targeted. To investigate the relevance of targeted therapy in patients with melanoma harboring RAF1 gene fusions, we reviewed records of 1268 melanoma patients with targeted sequencing data at the Dana-Farber Cancer Institute.

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Article Synopsis
  • The study revealed that melanoma only formed in zebrafish melanocytes lining internal organs, mirroring the conditions in human patients and highlighting a distinct chromatin structure compared to skin melanomas.
  • The findings indicated that zebrafish internal melanocytes share gene expression patterns with human MMs, showing characteristics linked to increased metastasis and decreased response to immunotherapy, thereby providing a valuable model for developing new treatments for MM.
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In the first of many thematic issues marking the 30 anniversary of Cell Chemical Biology, we highlight the contribution of chemical biology to RNA biology in a special issue on RNA modulation. We asked several leaders in the field to share their opinions on the current challenges and opportunities in RNA biology.

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RNA surveillance pathways detect and degrade defective transcripts to ensure RNA fidelity. We found that disrupted nuclear RNA surveillance is oncogenic. Cyclin-dependent kinase 13 () is mutated in melanoma, and patient-mutated accelerates zebrafish melanoma.

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Background: The use of targeted therapies and immune checkpoint inhibitors has drastically changed the management of patients with melanoma and brain metastases. Specifically, combination therapy with ipilimumab, a cytotoxic T-lymphocyte antigen 4 inhibitor, and nivolumab, a programmed cell death protein 1 inhibitor, has become a preferred systemic therapy option for patients with melanoma and asymptomatic brain metastases. However, the efficacy and toxicity profile of these agents in combination with brain-directed radiation therapy is not well described.

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  • * The WNT/β-catenin pathway is significantly affected by G9a abnormalities, as G9a suppresses the WNT antagonist DKK1, contributing to tumor development.
  • * Targeting mutated or amplified G9a could be an effective therapeutic strategy, as studies show it can promote a more immune-responsive "hot" tumor environment in melanoma and other cancers.
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In adult stem cell lineages, progenitor cells commonly undergo mitotic transit amplifying (TA) divisions before terminal differentiation, allowing production of many differentiated progeny per stem cell division. Mechanisms that limit TA divisions and trigger the switch to differentiation may protect against cancer by preventing accumulation of oncogenic mutations in the proliferating population. Here we show that the switch from TA proliferation to differentiation in the Drosophila male germline stem cell lineage is mediated by translational control.

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A key feature of many adult stem cell lineages is that stem cell daughters destined for differentiation undergo several transit amplifying (TA) divisions before initiating terminal differentiation, allowing few and infrequently dividing stem cells to produce many differentiated progeny. Although the number of progenitor divisions profoundly affects tissue (re)generation, and failure to control these divisions may contribute to cancer, the mechanisms that limit TA proliferation are not well understood. Here, we use a model stem cell lineage, the Drosophila male germ line, to investigate the mechanism that counts the number of TA divisions.

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Disruption of the dopamine (DA) transporter (Dat1) gene in mice leads to a 50% reduction or complete elimination of Dat1 expression in striatum of respective heterozygous (HZ) and knockout (KO) mice. Compared to wild-type (WT) controls, extracellular DA is increased approximately two- and five-fold in the mutants. Although open field (OF) activity is similar for WT and HZ animals, it is enhanced for KO mice.

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