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• W2894731098 abstract "Dedifferentiated chondrosarcoma is a rare bone sarcoma, whose genetic background remains incompletely understood. Mutations in SUZ12 or EED, which encode polycomb repressive complex 2 (PRC2) components, and resulting deficiency in H3K27me3 are characteristic features of the majority of malignant peripheral nerve sheath tumors. Here, we investigated H3K27me3 and PRC2 status in dedifferentiated chondrosarcoma. Among 19 evaluable dedifferentiated chondrosarcoma cases, six (32%) showed immunohistochemical loss of H3K27me3 only in the dedifferentiated component, whereas the well-differentiated component retained H3K27me3. H3K27me3-deficient dedifferentiated chondrosarcoma occurred in two men and four women with a median age of 66. All of these tumors affected bones of the upper half of the body, with the ribs being preferentially involved, which represented a significantly different distribution compared to that in the 13 H3K27me3-intact dedifferentiated chondrosarcomas. H3K27me3-deficient dedifferentiated chondrosarcomas were histologically different from H3K27me3-intact dedifferentiated chondrosarcomas, as the former invariably demonstrated dedifferentiated histology with a striking similarity to classic malignant peripheral nerve sheath tumor, comprising sweeping to swirling fascicles of relatively uniform spindle cells. Heterologous rhabdomyoblastic differentiation, the focal presence of grade 3 chondrosarcoma histology, and a cartilaginous component in the metastatic sites were exclusively seen in some cases of H3K27me3-deficient dedifferentiated chondrosarcoma. In all three H3K27me3-deficient dedifferentiated chondrosarcomas that contained focal grade 3 histology, dedifferentiated components did not juxtapose to the grade 3 areas but transitioned abruptly from the grade 1–2 components. Targeted next generation sequencing, which was successfully performed on four H3K27me3-deficient dedifferentiated chondrosarcomas, identified an IDH2 mutation in one case and COL2A1 truncations in three cases. The dedifferentiated areas of three cases harbored SUZ12 or EED alterations, which were absent in the well-differentiated component, suggesting a role for PRC2 aberrations in dedifferentiation. H3K27me3 deficiency defines a novel subset of dedifferentiated chondrosarcoma that requires recognition because of its diagnostic and potential clinical implications." @default.
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• W2894731098 date "2019-03-01" @default.
• W2894731098 modified "2023-10-07" @default.
• W2894731098 title "H3K27me3 deficiency defines a subset of dedifferentiated chondrosarcomas with characteristic clinicopathological features" @default.
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• W2894731098 doi "https://doi.org/10.1038/s41379-018-0140-5" @default.
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