Re-classification for therapeutic application in SMARCB1/INI1 deficient tumors

2013 Fiscal Year Final Research Report

• Project/Area Number: 24790352
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human pathology
• Research Institution: Kyushu University
• Principal Investigator: KOHASHI Kenichi 九州大学, 大学病院, 講師 (10529879)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 悪性ラブドイド腫瘍 / 類上皮肉腫 / SMARCB1/INI1 / Akt-mTOR

Research Abstract

Pediatric SMARCB1/INI1 (INI1)-deficient tumors were able to be re-classified into the three groups: conventional type, atypical teratoid/rhabdoid (AT/R) type and small cell type. Activation in Akt-mTOR pathway was found more frequently in AT/R and small cell types than in conventional type. Meanwhile, in most cases of epithelioid sarcoma (ES) including both conventional and proximal types, the Akt-mTOR pathway was activated.
It is suggested that mTOR inhibition is a potential treatment option for AT/R and small cell types of pediatric INI1-deficient tumor and ES. ES and malignant rhabdoid tumor are suggested to be distinct tumor entities.

Research Products

• [Journal Article] Phosphorylation of signal tr ansducer and activator of transcription 3 in soft tissue leiomyosarcoma is associated with a better prognosis (2013)
  • Author(s): Setsu N, Kohashi K, et al
  • Journal Title: Int J Cancer Volume: 132(1) Pages: 109-15
  • DOI: 10.1002/cncr.28255.
  • Peer Reviewed
• [Journal Article] Glypican 3 expression in tumors with loss of SMARCB1/ INI1 protein expression (2013)
  • Author(s): Kohashi K , Nakatsura T, et al
  • Journal Title: Hum Pathol Volume: 4 4(4) Pages: 526-33
  • DOI: 10.1002/cncr.28255.
  • Peer Reviewed
• [Journal Article] Fascin-1 overexpression and miR-133b downregulation in the pro gression of gastrointestinal stromal t umor (2013)
  • Author(s): Yamamoto H, Kohashi K, et al
  • Journal Title: Mod Pathol Volume: 26(4) Pages: 563-71
  • DOI: 10.1038/modpathol.2012.198
  • Peer Reviewed
• [Journal Article] Prognostic significance of AKT /mTOR and MAP K pathways and antitumor effect of mTOR inhibitor in NF1-related and sporadic malignant peripheral nerve sheath tumors (2013)
  • Author(s): Endo M, Yamamoto H, Setsu N, Kohashi K, et al
  • Journal Title: Clin Cancer Res Volume: 19(2) Pages: 450-61
  • DOI: 10.1158/1078-0432.CCR-12-1067
  • Peer Reviewed
• [Journal Article] Mutual regulation between Raf/MEK/ERK signaling and Y-box-binding protein-1 promotes prostate cancer progression (2013)
  • Author(s): Imada K, Shiota M, Kohashi K, et al
  • Journal Title: Clin Cancer Res Volume: 19(17) Pages: 4638-50
  • DOI: 10.1158/1078-0432.CCR-12-3705
  • Peer Reviewed
• [Journal Article] Prognostic impact of the activation status of the Akt/mTOR pathway in synovial sarcoma (2013)
  • Author(s): Setsu N, Kohashi K, et al
  • Journal Title: Cancer Volume: 119(19) Pages: 3504-13
  • DOI: 10.1002/cncr.28255
  • Peer Reviewed
• [Journal Article] An augmented reality navigation system for pediatric oncologic surgery based on preoperative CT and MRI images (2013)
  • Author(s): Souzaki R, Ieiri S, Uemura M, Ohuchida K, Tomikawa M, Kinoshita Y, Koga Y, Suminoe A, Kohashi K, et al
  • Journal Title: J Pediatr Surg Volume: 48(12) Pages: 2479-83
  • DOI: 10.1016/j.jpedsurg.2013.08.025
  • Peer Reviewed
• [Journal Article] The Akt/mammalian target of rapamycin pathway is activated and associated with adverse prognosis in soft tissue leiomyosarcomas (2012)
  • Author(s): Setsu N, Yamamoto H, Kohashi K, et al
  • Journal Title: Cancer Volume: 118(6) Pages: 1637-48
  • DOI: 10.1002/cncr.26448
  • Peer Reviewed
• [Journal Article] Inhibin-αand synaptophysin immunoreactivity in synovial sarcoma with granular cell features (2012)
  • Author(s): Setsu N, Kohashi K, et al
  • Journal Title: Hum Pathol Volume: 43(6) Pages: 850-7
  • DOI: 10.1016/j.humpath.2011.07.012
  • Peer Reviewed
• [Journal Article] Surgical intervention strategies for pediatric ovarian tumors : experience with 60 cases at one institution (2012)
  • Author(s): Tajiri T, Souzaki R, Kinoshita Y, Yosue R, Kohashi K, et al
  • Journal Title: Pediatr Surg Int Volume: 28(1) Pages: 27-31
  • DOI: 10.1007/s00383-011-3004-4
  • Peer Reviewed
• [Journal Article] A morphological study of the removed livers from patients receiving living donor liver transplantation for adult biliary atresia (2012)
  • Author(s): Matsuura T, Kohashi K, et al
  • Journal Title: Pediatr Surg Int Volume: 28(12) Pages: 1171-5
  • DOI: 10.1007/s00383-012-3183-7
  • Peer Reviewed
• [Journal Article] Surgical strategies for unresectable hepatoblastomas (2012)
  • Author(s): Tajiri T, Kimura O, Fumino S, Furukawa T, Iehara T, Souzaki R, Kinoshita Y, Koga Y, Suminoe A, Hara T, Kohashi K, et al
  • Journal Title: J Pediatr Surg Volume: 47(12) Pages: 2194-8
  • DOI: 10.1016/j.jpedsurg.2012.09.007
  • Peer Reviewed
• [Journal Article] The prognostic significance of blastemal predominant histology in initially resected Wilms' tumors : A report from the Study Group for Pediatric Solid Tumors in the Kyushu Area, Japan (2012)
  • Author(s): Kinoshita Y, Suminoe A, Inada H, Yagi M, Yanai F, Zaizen Y, Nishi M, Inomata Y, Kawakami K, Matsufuji H, Suenobu S, Handa N, Kohashi K, et al
  • Journal Title: J Pediatr Surg Volume: 47(12) Pages: 2205-9
  • DOI: 10.1016/j.jpedsurg.2012.09.010
  • Peer Reviewed
• [Journal Article] Differential microRNA expres sion profiles between malignant rhabdoid tumor and epithelioid sarcoma : miR193a-5p is sugge sted to downregulate SMARCB1 m RNA expression
  • Author(s): Kohashi K , Yamamoto H , et al
  • Journal Title: Mod Pathol Volume: 20131129
  • DOI: 10.1038/modpathol.2013.213
  • Peer Reviewed
• [Presentation] 小児軟部腫瘍 (2013)
  • Author(s): 孝橋賢一、山元英崇、山田裕一、小田義直
  • Organizer: 第55回日本小児血液・がん学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2013-11-29
• [Presentation] 類上皮肉腫におけるAkt/mTOR経路関連蛋白の発現検討 (2013)
  • Author(s): 孝橋賢一、髙橋祐介、山田裕一、石井武彰、井浦国生、前川啓、山元英崇、岩本幸英、小田義直
  • Organizer: 第46回日本整形外科学会骨軟部腫瘍学術集会
  • Place of Presentation: 東京
  • Year and Date: 2013-07-11
• [Presentation] 小児軟部腫瘍のゲノミクス (2013)
  • Author(s): 孝橋賢一、山元英崇、山田裕一、小田義直
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2013-06-07
• [Presentation] Art-mTOR pathway Activation Analysis in Re-Classified Prediatric (2013)
  • Author(s): Kohashi K, Endo M, Setsu N, Takahashi Y, Yamada Y, Yamamoto H, Oda Y
  • Organizer: SMARCB1/INI1-Dedicient Tumor 2013 Annual Meeting of USCAP
  • Place of Presentation: Baltimore, Maryland
  • Year and Date: 2013-03-04
• [Presentation] Re-classification of pediatric SMARCB1/INI1-deficient tumor, according to microRNA and immunohistochemical expression (2012)
  • Author(s): Kohashi K, Kishimoto H, Tanaka Y, Yamada Y, Yamamoto H, Taguchi T, Oda Y
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 2012-09-20