Elucidation of crosstalk between pediatric cancers and neural development and its application for novel therapeutic strategies

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K19467
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 50:Oncology and related fields
• Research Institution: Kyoto University
• Principal Investigator: Takita Junko 京都大学, 医学研究科, 教授 (00359621)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Keywords: 小児がん / 発達障害 / 自閉症 / 神経芽腫 / Ewing肉腫

Outline of Final Research Achievements

To elucidate candidate common pathways in tumorigenesis and neural development, we performed exome sequencing of 2 mental retardation cases with neuroblastoma and Ewing sarcoma, respectively. In addition, we also analyzed open database (TARGET), in order to screen candidate genes in pediatric solid tumors. In neuroblastoma cases, a novel germline variant of CSMD2, a responsible gene for familial myoclonus epilepsy was identified. Of note, this gene was deleted in several tumor samples, suggesting that this gene would be involved not only in neural development but also tumor development. Furthermore, a novel germline mutation of CNTN6 was found in the Ewing sarcoma case, which is thought to be involved in the neural development and tumorigenesis of ovarian cancer. Thus, our results suggest that CSMD2 and CNTN6 are promising candidates which involved in the common pathways in development delay and tumorigenesis.

Free Research Field

小児がん

Academic Significance and Societal Importance of the Research Achievements

近年、発達障害の動物モデルが相次いで開発され、行動薬理学の研究は進められているものの、ヒトの発達障害の発症分子機構に基づいた本質的な薬物治療の開発に関する研究は、未だ発展途上であり、経験的な対症療法のみが行われているのが現状である。本研究成果によって、神経芽腫におけるCSMD2とEwing肉腫におけるCNTN6が、腫瘍の発生と神経発生の共通するパスウエイ遺伝子として同定されたが、これらを標的とした治療の開発は、腫瘍のみならず発達障害に対する根本的な治療の開発につながることが期待される。