样本编号	SAMC3096500
外部数据库编号	GSA-Human: HRS955020
样品名称	SJALL018368_D1
样本标题	SJALL018368_D1
样品类型	Human sample
物种名称	Homo sapiens
描述信息	Informed consents for research with tissue were obtained from parents for all patients. The research was approved by the Ethics Committee at Shanghai Children's Medical Center.
样本属性	*该样本包含更多受控访问信息，请通过GSA-Human系统申请项目HRA005668数据获取。
发布日期	2025-09-27
项目编号	PRJCA002230
提交者	Yu Liu (liuyu@scmc.com.cn)
提交单位	Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine
提交日期	2023-10-09

样本包含数据信息

资源名称	描述
GSA-Human (1)	-
HRA005668 (Controlled Access)	To study the mechanisms of relapse in acute lymphoblastic leukemia (ALL), we performed whole-genome sequencing of 103 diagnosis-relapse germline trios and ultra-deep sequencing of 208 serial samples in 16 patients. Relapse-specific somatic alterations were enriched in 12 genes involved in drug response. Convergent evolution, where multiple subclones harbor mutations in the same drug resistance gene, was observed in six relapses and confirmed by single-cell sequencing in one case. Mathematical modeling and mutational signature analysis indicated that early relapse resistance acquisition was frequently two-step process where a persistent clone survived initial therapy, and later acquired bona fide resistance mutations during therapy. The novel signatures were detected in 27% of relapsed ALLs and were responsible for 46% of acquired resistance mutations in NT5C2, PRPS1, NR3C1, and TP53. These results suggest that chemotherapy induced drug resistance mutations facilitate a subset of pediatric ALL relapses.

资源名称

描述

GSA-Human (1)

HRA005668 (Controlled Access)

To study the mechanisms of relapse in acute lymphoblastic leukemia (ALL), we performed whole-genome sequencing of 103 diagnosis-relapse germline trios and ultra-deep sequencing of 208 serial samples in 16 patients. Relapse-specific somatic alterations were enriched in 12 genes involved in drug response. Convergent evolution, where multiple subclones harbor mutations in the same drug resistance gene, was observed in six relapses and confirmed by single-cell sequencing in one case. Mathematical modeling and mutational signature analysis indicated that early relapse resistance acquisition was frequently two-step process where a persistent clone survived initial therapy, and later acquired bona fide resistance mutations during therapy. The novel signatures were detected in 27% of relapsed ALLs and were responsible for 46% of acquired resistance mutations in NT5C2, PRPS1, NR3C1, and TP53. These results suggest that chemotherapy induced drug resistance mutations facilitate a subset of pediatric ALL relapses.