Study

Mutational landscape and patterns of clonal evolution in relapsed pediatric acute lymphoblastic leukemia

Study ID Alternative Stable ID Type
EGAS00001003975 Other

Study Description

Relapse of acute lymphoblastic leukemia (ALL) remains a leading cause of childhood death. Prior studies have shown clonal mutations at relapse often arise from relapse-fated subclones that exist at diagnosis. However, the genomic landscape, evolutionary trajectories and mutational mechanisms driving relapse are incompletely understood. In an analysis of 92 cases of relapsed childhood ALL, incorporating multimodal DNA and RNA sequencing, deep digital mutational tracking and xenografting to formally define clonal structure, we identify 50 significant targets of mutation with distinct patterns of mutational acquisition or enrichment. CREBBP, NOTCH1, and Ras signaling mutations rose from diagnosis subclones, whereas variants in NCOR2, USH2A and NT5C2 were exclusively observed at relapse. Evolutionary modeling and xenografting demonstrated that relapse-fated clones were minor (50%), major (27%) or multiclonal (18%) at diagnosis. Putative second leukemias, including those with lineage shift, were shown to most commonly represent relapse from an ancestral clone rather than a truly ... (Show More)

Study Datasets 6 datasets.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001005506
WGS files for Mullighan_GL_reALL paper titled "Mutational landscape and patterns of clonal evolution in relapsed pediatric acute lymphoblastic leukemia"
Illumina HiSeq 2000 99
EGAD00001005509
WXS files for Mullighan_GL_reALL paper titled "Mutational landscape and patterns of clonal evolution in relapsed pediatric acute lymphoblastic leukemia"
Illumina HiSeq 2000 276
EGAD00001005510
RNAseq files for Mullighan_GL_reALL RNASEQ2 paper titled "Mutational landscape and patterns of clonal evolution in relapsed pediatric acute lymphoblastic leukemia"
Illumina HiSeq 2000 34
EGAD00001005511
RNASeq files for Mullighan_GL_reALL RNASEQ1 paper titled "Mutational landscape and patterns of clonal evolution in relapsed pediatric acute lymphoblastic leukemia"
Illumina HiSeq 2000 81
EGAD00010001813
Over 1.87 million SNP and CNV loci are screened by Affymetrix SNP 6.0 array
Affymetrix SNP 6.0 array 91
EGAD00010001814
Over 1.87 million SNP and CNV loci are screened by Affymetrix SNP 6.0 array
Affymetrix SNP 6.0 array 195

Who archives the data?

There are no publications available