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

Project Data

Resource name Description