RAG mediated recombination is the predominant driver of oncogenic rearrangement in ETV6-RUNX1 Acute Lymphoblastic Leukemia (Rearrangement_sequencing_data)
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.
- Technologies: Illumina Genome Analyzer II, Illumina HiSeq 2000
- 50 samples
- DAC: EGAC00001000000
- Data Use Conditions:
- IS DUO:0000028 (version: 2021-02-23) institution specific restriction This data use modifier indicates that use is limited to use within an approved institution.
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- GRU DUO:0000042 (version: 2021-02-23) general research use This data use permission indicates that use is allowed for general research use for any research purpose.
- PUB DUO:0000019 (version: 2021-02-23) publication required This data use modifier indicates that requestor agrees to make results of studies using the data available to the larger scientific community.
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