RAG mediated recombination is the predominant driver of oncogenic rearrangement in ETV6-RUNX1 Acute Lymphoblastic Leukemia (Whole exome sequencing data)

Dataset ID Technology Samples
EGAD00001000636 Illumina Genome Analyzer II 117

Dataset Description

The ETV6-RUNX1 fusion gene, found in 25% of childhood acute lymphoblastic leukemia (ALL), is acquired in utero but requires additional somatic mutations for overt leukemia. We used exome and low-coverage whole-genome sequencing to characterize the critical secondary events associated with leukemic transformation. RAG-mediated deletions emerge as the dominant mutational process, accounting for at least 43% of genomic rearrangements and characterized by the presence of recombination signal sequence motifs near the breakpoints; incorporation of non-templated sequence at the junction and a ten-fold enrichment at promoters and enhancers of genes actively transcribed in early B-lineage development. Single-cell tracking shows that this mechanism is not restricted to one founder cell but is rather active throughout leukemic evolution. Integration of point mutation and rearrangement data identifies recurrent inactivation of ATF7IP and MGA as two new tumor suppressor genes.Thus, a remarkably parsimonious mutational process transforms ETV6-RUNX1 lymphoblasts, striking promoters and enhancers of the genes that normally control B-cell differentiation.

Data Use Conditions


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Label Code Version Modifier
general research use DUO:0000042 2021-02-23
institution specific restriction DUO:0000028 2021-02-23
publication required DUO:0000019 2021-02-23
user specific restriction DUO:0000026 2021-02-23