Comprehensive and spationtemporal genetic analyses of clonal evolution of metastatic and recurrent pediatric solid tumors

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293242
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: The University of Tokyo
• Principal Investigator: Takita Junko 東京大学, 医学部附属病院, 准教授 (00359621)
• Co-Investigator(Kenkyū-buntansha): 加藤 元博 国立研究開発法人国立成育医療研究センター, 小児がんセンター 移植・細胞治療科, 医長 (40708690) ; 安戸 裕貴 東京大学, 医学部附属病院, 助教 (70422285)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 小児固形腫瘍 / 膵芽腫 / クローン進化 / β―カテニン

Outline of Final Research Achievements

To explore recurrent gene mutations in PBL, we performed Whole exome sequencing (WES) on paired tumor-normal DNA samples from one refractory case (PBL001). Seven spatially separated tumor samples resected at 3 different time points were used for WES. All metastatic samples in a case (PBL001) showed higher frequencies of mutations (mean number = 61.2). Notably, among the 240 mutated genes, no additional genes other than CTNNB1 were recurrently altered, confirming the obvious impact of CTNNB1 mutations in PBL pathogenesis. Likewise, 11p uniparental disomy (UPD) was also detected all samples examined. Sequencing of multiple samples from PBL001 revealed intra-tumor heterogeneity within primary and metastatic sites, as well as clonal evolution with a truncal CTNNB1 mutation and 11p UPD. Importantly, a truncal CTNNB1 mutation and 11p UPD provided further evidence that a CTNNB1 mutation was likely to be virtually necessary for development and progression of PBL.

Free Research Field

小児固形腫瘍