| Accession |
PRJCA002230 |
| Title |
Therapy-induced mutations drive the genomic landscape of relapsed acute lymphoblastic leukemia |
| Relevance |
Medical |
| Data types |
Whole genome sequencing
Transcriptome or Gene expression
|
| Organisms |
Homo sapiens
|
| Description |
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. |
| Sample scope |
Multiisolate |
| Release date |
2022-03-03 |
| Publication |
| PubMed ID |
Article title |
Journal name |
DOI |
Year |
| 6940198
|
|
|
|
|
|
|
| Grants |
| Agency |
program |
Grant ID |
Grant title |
| 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
|
|
|
|
| Submitter |
Yu
Liu (liuyu@scmc.com.cn)
|
| Organization |
Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine |
| Submission date |
2020-02-17 |
