Novel molecular sub-classification of soft tissue sarcomas

• Project/Area Number: 18K16660
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Kobe University
• Principal Investigator: Komatsu Masato 神戸大学, 医学部附属病院, 助教 (50531753)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 軟部腫瘍 / 肉腫 / 癌精巣抗原 / 腫瘍精巣抗原 / 融合遺伝子 / がん精巣抗原 / 分子マーカー / 免疫組織染色

Outline of Final Research Achievements

In soft tissue sarcomas, there is no objective and reproducible molecular markers predicting its malignant potential. To uncover the molecular sub-classification of soft tissue sarcomas according to the expression of cancer-testis antigens (CTAs), which were statistically extracted from publicly available gene-expression database, we performed immunohistochemical analyses of these CTAs using surgically resected sarcoma specimens.
As a result, the higher nuclear expression of DEPDC1A was tend to be associated with shorter progression free survival of patients with leiomyosarcomas and also to be associated with the increased necrotic burden and Ki-67 labeling index, which implying that DEPDC1A is involved in intrinsic malignant manifestation of leiomyosarcomas. As DEPDC1A had been shown to play a critical role for positive regulations in NFKB pathways, DEPDC1A is not only useful for predicting malignant potential, but also would be attractive therapeutic target.

Academic Significance and Societal Importance of the Research Achievements

悪性腫瘍である肉腫は希少腫瘍の一つで、これまでその悪性度を予測する客観的な分子マーカーの研究・あるいは治療標的の開発が癌腫に比べてが進んでいないことが問題であった。
我々は癌精巣抗原という、精巣と悪性腫瘍でのみ発現がみられる分子に着目したわけだが、1)正常組織では精巣以外の臓器では非常に発現レベルが低く、2)治療標的となった場合に副作用の低減が期待されるという理由がその着眼理由である。
実際DEPDC1Aの高発現が平滑筋肉腫でその悪性度と関連しうることが示され、すでにDEPDC1Aをターゲットとした治療標的の基礎的研究も進んでいることより、平滑筋肉腫の新たな治療展開が期待される。

Research Products

• [Journal Article] Soft tissue tumor with novel NR1D1-MAML1 fusion in a pediatric case (2020)
  • Author(s): Komatsu M, Yamamoto N, Kawamoto T, Kawakami Y, Hara H, Uemura S, Nishimura N, Akisue T, Kuroda R, Iijima K, Jimbo N, Kanzawa M, Kajimoto K, Itoh T, Hirose T.
  • Journal Title: Virchows Archiv Volume: 477 Issue: 6 Pages: 891-895
  • DOI: 10.1007/s00428-020-02838-0
  • Peer Reviewed
• [Journal Article] EWSR1‐CREM fusion in pulmonary mesenchymal neoplasm showing distinctive clear cell morphology (2020)
  • Author(s): Komatsu M, Sakai Y, Nishikubo M, Tane S, Nishio W, Kajimoto K, Hirose T.
  • Journal Title: Pathology International Volume: 70 Issue: 12 Pages: 1020-1026
  • DOI: 10.1111/pin.13030
  • Peer Reviewed
• [Journal Article] Intracranial myxoid mesenchymal tumor with EWSR1?CREB1 gene fusion: a case report and literature review (2020)
  • Author(s): Komatsu M, Yoshida A, Tanaka K, Matsuo K, Sasayama T, Kojita Y, Kanda T, Kodama Y, Itoh T, Hirose T.
  • Journal Title: Brain Tumor Pathology Volume: 37 Issue: 2 Pages: 76-80
  • DOI: 10.1007/s10014-020-00359-x
  • Peer Reviewed
• [Journal Article] A novel EWSR1-VGLL1 gene fusion in a soft tissue malignant myoepithelial tumor. (2020)
  • Author(s): Komatsu M, Kawamoto T, Kanzawa M, Kawakami Y, Hara H, Akisue T, Kuroda R, Nakamura H, Hokka D, Jimbo N, Itoh T, Hirose T.
  • Journal Title: Genes Chromosomes Cancer Volume: 59 Issue: 4 Pages: 249-254
  • DOI: 10.1002/gcc.22823
  • Peer Reviewed
• [Journal Article] Anaplastic Carcinoma Arising From Ovarian Mucinous Adenocarcinoma With Massive Cardiopulmonary Metastasis: An Autopsy Case Report. (2019)
  • Author(s): Kihara T, Komatsu M, Sakuma T, Mikami Y, Takasu K, Nakashima Y, Mochizuki S, Maruo M.
  • Journal Title: Journal of Obstetrics and Gynaecology Canada Volume: 41 Issue: 1 Pages: 72-75
  • DOI: 10.1016/j.jogc.2018.07.014
  • Peer Reviewed
• [Journal Article] A rare autopsy case of epithelioid angiosarcoma arising in the aorta in a patient with massive multi-organ embolization. (2018)
  • Author(s): Komatsu M, Hashimoto T, Hanioka K, Itoh T, Hirose T.
  • Journal Title: Pathology International Volume: 68 Issue: 10 Pages: 574-576
  • DOI: 10.1111/pin.12690
  • Peer Reviewed
• [Presentation] Myxoid angiomatoid fibrous histiocytomaに類似した組織像を呈するEWSR1遺伝子再構成を伴った頭蓋内腫瘍の1例 (2020)
  • Author(s): 小松正人、吉田朗彦、松尾和哉、篠山隆司、児玉良典、伊藤智雄、廣瀬隆則
  • Organizer: 第109回日本病理学会学術集会
• [Presentation] Interventional Oncologistとして知っておくべきがんゲノム診療の現状と課題 (2020)
  • Author(s): 小松正人
  • Organizer: 第49回日本IVR学会総会
  • Invited
• [Presentation] 異型多形脂肪腫性腫瘍と考えられた1例 (2018)
  • Author(s): 小松 正人、阿部 志保、西尾 祐美、原 仁美、神澤 真紀、伊藤 智雄、廣瀬 隆則
  • Organizer: 第107回日本病理学会総会