AntiCancer Inc, San Diego, CA, U.S.A.
Department of Surgery, University of California San Diego, La Jolla, CA, U.S.A.
Cancer Genomics Proteomics. 2021 Nov-Dec;18(6):715-721. doi: 10.21873/cgp.20292.
BACKGROUND/AIM: Sarcomas are considered a heterogeneous disease with incomplete understanding of its molecular basis. In the present study, to further understand general molecular changes in sarcoma, patient-derived xenograft (PDX) mouse models of the three most common soft-tissue sarcomas: myxofibrosarcoma, undifferentiated pleomorphic sarcoma (UPS) and liposarcoma were established and the methylation status of histone H3 lysine marks was studied.
Immunoblotting and immunohistochemical staining were used to quantify the extent of methylation of histone H3K4me3 and histone H3K9me3.
In all 3 sarcoma types in PDX models, histone H3K4me3 and H3K9me3 were found highly over-methylated compared to normal muscle tissue.
Histone H3 lysine over-methylation may be a general basis of malignancy of the major sarcoma types.
背景/目的:肉瘤被认为是一种具有异质性的疾病,其分子基础尚未完全了解。在本研究中,为了进一步了解肉瘤的一般分子变化,建立了三种最常见的软组织肉瘤:黏液纤维肉瘤、未分化多形性肉瘤(UPS)和脂肪肉瘤的患者来源异种移植(PDX)小鼠模型,并研究了组蛋白 H3 赖氨酸标记的甲基化状态。
使用免疫印迹和免疫组织化学染色来定量组蛋白 H3K4me3 和组蛋白 H3K9me3 的甲基化程度。
在 PDX 模型中的所有 3 种肉瘤类型中,与正常肌肉组织相比,组蛋白 H3K4me3 和 H3K9me3 被发现高度过度甲基化。
组蛋白 H3 赖氨酸过度甲基化可能是主要肉瘤类型恶性肿瘤的一般基础。