Clinicopathological and molecular characterization of bone and soft tissue tumors with aberrant histone modification

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K15110
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: The University of Tokyo (2019); National Cancer Center Japan (2018)
• Principal Investigator: MAKISE Naohiro 東京大学, 大学院医学系研究科(医学部), 助教 (70815373)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 肉腫 / 病理 / 脱分化 / 異所性分化 / ヒストン / 免疫染色 / FISH / 次世代シーケンサー

Outline of Final Research Achievements

We discovered that SUZ12 or EED mutation and H3K27me3 loss, which were thought to be specific for malignant peripheral nerve sheath tumors, were also seen in subsets of dedifferentiated liposarcomas, extraskeletal osteosarcomas, and dedifferentiated chondrosarcomas. H3K27me3 loss was associated with heterologous differentiation.
We discovered a case of low-grade endometrial stromal sarcoma with a novel fusion of histone modifiers, MEAF6 and SUZ12. We also discovered two cases of mesenchymal tumors with RREB1-MRTFB fusion involving the mediastinum.

Free Research Field

病理診断学

Academic Significance and Societal Importance of the Research Achievements

SUZ12,EED遺伝子変異とH3K27me3消失が悪性末梢神経鞘腫瘍以外の骨軟部腫瘍でも見られることを発見した。これにより、H3K27me3消失が色々な腫瘍の脱分化や異所性分化に関わっていること、診断の際に注意が必要なことを明らかにした。SUZ12,EED遺伝子変異は、治療標的の候補となる可能性がある。
新規融合遺伝子MEAF6-SUZ12を有する低悪性度子宮内膜間質肉腫1例と、頭頚部外発生のRREB1-MRTFB融合間葉系腫瘍2例を報告し、骨軟部腫瘍のより適切な分類に寄与した。