Over-methylation of Histone H3 Lysines Is a Common Molecular Change Among the Three Major Types of Soft-tissue Sarcoma in Patient-derived Xenograft (PDX) Mouse Models
YUSUKE AOKI, Jun Yamamoto, Yasunori Tome, Kazuyuki Hamada, NORIYUKI MASAKI, Sachiko Inubushi, Yoshihiko Tashiro, Michael Bouvet, Itaru Endo, Kotaro Nishida, Robert M. Hoffman
Abstract
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. MATERIALS AND METHODS: Immunoblotting and immunohistochemical staining were used to quantify the extent of methylation of histone H3K4me3 and histone H3K9me3. RESULTS: In all 3 sarcoma types in PDX models, histone H3K4me3 and H3K9me3 were found highly over-methylated compared to normal muscle tissue. CONCLUSION: Histone H3 lysine over-methylation may be a general basis of malignancy of the major sarcoma types.