Clinicopathological and molecular characterization of tumors with various directions of differentiation

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16167
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Chiba Cancer Center (Research Institute) (2021-2022); The University of Tokyo (2020)
• Principal Investigator: MAKISE Naohiro 千葉県がんセンター(研究所), 臨床病理部, 医長 (70815373)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 肉腫 / 病理

Outline of Final Research Achievements

I found FOS gene rearrangement in proliferative fasciitis/myositis. I found a homozygous deletion of the EED gene and loss of H3K27me3 in dedifferentiated chordomas with heterologous rhabdomyoblastic differentiation. I found the EWSR1::NFATC2 fusion gene and characteristic radiological features in a sarcoma previously diagnosed as Ewing-like adamantinoma. I reported a DICER1 mutant sarcoma showing differentiation into rhabdomyosarcoma.
I have also been involved in other reports of RREB1::MRTFB tumors, NTRK-rearranged mesenchymal neoplasms, phosphaturic mesenchymal tumors, and epithelioid hemangioendotheliomas with neuroendocrine differentiation.

Free Research Field

人体病理学

Academic Significance and Societal Importance of the Research Achievements

本研究により様々な分化方向を示すような腫瘍の臨床病理像、分子異常を明らかにした。EWSR1::NFATC2肉腫に特徴的な放射線像を報告した。DICER1変異肉腫に特徴的な臨床像、組織像を報告した。増殖性筋膜炎/筋炎におけるc-FOS免疫染色、脱分化型脊索腫におけるH3K27me3免疫染色などの診断的有用性を報告した。また、リン酸塩尿性間葉系腫瘍やNTRK融合腫瘍の臨床病理放射線像の報告にも携わった。これらは正確な病理診断に寄与することが期待できる。
NTRK融合腫瘍には標的治療が期待できる。DICER1変異肉腫やH3K27me3消失脱分化型脊索腫に対する標的治療の可能性についても論じた。