Investigation for hidden cancer predisposition in pediatric cancer

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K22608
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 52:General internal medicine and related fields
• Research Institution: The University of Tokyo (2020); National Center for Child Health and Development (2019)
• Principal Investigator: Kato Motohiro 東京大学, 医学部附属病院, 教授 (40708690)
• Co-Investigator(Kenkyū-buntansha): 樋渡 光輝 東京大学, 医学部附属病院, 講師 (40597126)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Keywords: 癌

Outline of Final Research Achievements

Intensive analysis of the SMARCB1 gene in malignant rhabdoid tumors (MRT) revealed eight of 16 patients with germline genetic variants. Three patients had mosaicism of the variants, which conventional methods might overlook. The prevalence of cancer predisposition in MRT may thus be higher than previously reported.
We next focused on prevalence of germline variants of GATA2 and SAMD9/9L in hematologic disorder with monosomy 7. A total of 25 patients were analyzed, and seven patients with a germline pathogenic GATA2 variant were found. For SAMD9/9L screening, next-generation sequencing was used to detect low-abundance variants and found four novel germline variants. Functional analysis revealed that three out of the four variants showed functional abnormality. GATA2 and SAMD9/9L were sequenced in 25 patients with pediatric hematologic disorders associated with -7, and 40% of them were found to have some pathogenic germline variants in the three genes.

Free Research Field

小児がん

Academic Significance and Societal Importance of the Research Achievements

これらの研究により、小児がんの発症や臨床経過において遺伝的な背景の役割が重要であることが確認された。