Elucidation of Tumor Progression Mechanisms through Telomere Maintenance Mechanisms in Myxoid Liposarcoma

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K16570
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: YAMASHITA Kyoko 公益財団法人がん研究会, 有明病院 病理部, 副医長 (50754975)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: テロメア維持機構 / 粘液型脂肪肉腫

Outline of Final Research Achievements

We performed a clinicopathological study and analyzed the mechanism of telomere maintenance in myxoid liposarcoma. Tumor size, FNCLCC grade, and necrosis were associated with prognosis, while hotspot mutations in the TERT promoter (C228T or C250T), which were observed in more than 70% of the cases, were not associated with prognosis. All of the hotspot mutation-negative cases also showed TERT mRNA expression, and seven cases (47%) of them showed the same level of TERT mRNA expression as the positive cases. Among the 19 cases without hotspot mutation, chromosomal rearrangements around TERT were observed in three cases, and mutations in other locations of the TERT promoter (A161C, C237G) were observed in two cases. In conclusion, TERT abnormalities in myxoid liposarcoma should not be a secondary phenomenon associated with malignancy, but may be an early event which would be important in tumorigenesis.

Free Research Field

Pathology of bone and soft tissue tumors

Academic Significance and Societal Importance of the Research Achievements

実験結果を総合すると、他の多くの腫瘍とは異なり、粘液型脂肪肉腫におけるTERT異常は、悪性度と関連するような2次的な現象ではなく、腫瘍発生の早期に生じ、腫瘍形成に重要な現象である可能性が考えられた。さらに、TERTプロモーターのhotspot変異以外にも、TERTプロモーターの別箇所での変異や、TERT付近での染色体再構成によってTERTの高発現をきたす機序を示した。腫瘍形成におけるTERTの役割について新たな観点が得られたとともに、TERT発現上昇をきたす分子機構についても明らかになった。