| 项目编号 |
PRJCA002230 |
| 项目标题 |
Therapy-induced mutations drive the genomic landscape of relapsed acute lymphoblastic leukemia |
| 涉及领域 |
Medical |
| 数据类型 |
Whole genome sequencing
Transcriptome or Gene expression
|
| 物种名称 |
Homo sapiens
|
| 描述信息 |
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. |
| 样品范围 |
Multiisolate |
| 发布日期 |
2022-03-03 |
| 出版信息 |
|
| 项目资金来源 |
| 机构 |
项目类型 |
授权项目ID |
授权项目名称 |
| Cancer Center Support Grant
|
|
P30CA021765
|
|
| Viva China Children Cancer Foundation
|
|
16CR2024A
|
|
| National Natural Science Foundation of China (NSFC)
|
|
31530017
|
|
| National Natural Science Foundation of China (NSFC)
|
|
81670174
|
|
| National Natural Science Foundation of China (NSFC)
|
|
81670136
|
|
| National Natural Science Foundation of China (NSFC)
|
|
81470313
|
|
| Science and Technology Commission of Pudong New Area Foundation
|
|
PKJ2014Y02
|
|
|
|
| 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 |
2020-02-17 |
