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HRA005668

HRA005668.xlsx

Title:

Whole genome sequencing of 32 childhood ALL patients

Release date:

2023-10-09

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.

Data Accessibility:

Controlled access Request Data

BioProject:

PRJCA002230

Study type:

Disease Study

Disease name:

acute lymphocytic leukemia

Data Access Committee

For each controlled access study, there is a corresponding Data Access Committee(DAC) to determine the access permissions. Access to actual data files is not managed by NGDC.

DAC NO.:

HDAC000054

DAC name:

SCMC

Contact person:

Liu Yu

Email:

liuyu@scmc.com.cn

Description:

Shanghai Children's Medical Center

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