The genomic basis of childhood T-lineage acute lymphoblastic leukemia 0 Visualizations

Mullighan Lab
0
1.4K

T-lineage acute lymphoblastic leukemia (T-ALL) is a high-risk tumor that has eluded comprehensive genomic characterization, in part due to the high frequency of non-coding genomic alterations resulting in oncogene deregulation. Here we report integrated genome and transcriptome sequencing of T-ALL tumor and remission samples obtained from over 1300 uniformly treated children with T-ALL, coupled with epigenomic and single cell analysis of malignant and normal T cell precursors. Integrated analysis identified 15 subtypes with distinct genomic drivers, gene expression, developmental state and outcome. Integration with chromatin topology analyses enabled elucidation of multiple mechanisms of enhancer deregulation that involve enhancers and genes in a subtype-specific fashion, demonstrating a wide-spread involvement of the noncoding genome that has not been systematically interrogated in prior studies. We show that the immunophenotypically-described, high-risk entity of early T-cell precursor ALL is superseded by a broader category of “ETP-like” leukemia with variable immunophenotype and diverse genomic alterations of a core set of genes encoding regulators of hematopoietic stem cell development. Numerous genetic alterations and disease subtypes emerged as independent predictors of survival and treatment failure in univariable and multivariable outcome models. These findings provide a roadmap for the classification, risk stratification and mechanistic understanding of this disease.

Loading Visualizations
Approved - edits can only be made to update the visibility. Cannot change visibility after setting to public.
Whole Genome Sequencing
RNA Sequencing
ATAC Sequencing
HiChIP
hg38 / GRCh38
PATFWF BCL11B::HOXB13 Translocation
Oct 5, 2023
0
< 1k
PRIVATE

Depiction of H3K27ac HiChIP, H3K27ac Coverage, Diagnostic Sample, and Germline WGS/WTS Coverage in a T-ALL patient, showcasing interactions between HOXB13 BCL11B Translocation. Heatmap represent interactions between genomic loci, with color coding denoting int...

Mullighan Lab

 
Approved - edits can only be made to update the visibility. Cannot change visibility after setting to public.
Whole Genome Sequencing
RNA Sequencing
ATAC Sequencing
HiChIP
hg38 / GRCh38
PATHJF CASC15/SOX4::HOXA13 Translocation
Oct 5, 2023
0
< 1k
PRIVATE

Depiction of H3K27ac HiChIP, H3K27ac coverage, diagnostic/germline sample WGS and WTS coverage in a T-ALL patient, showcasing enhancer hijacking of the CASC15/SOX4 enhancers by HOXA13. The heatmap represent interactions between genomic loci, with color coding...

Mullighan Lab

 
Approved - edits can only be made to update the visibility. Cannot change visibility after setting to public.
Whole Genome Sequencing
hg38 / GRCh38
T-ALL Genomic Data
Oct 5, 2023
0
< 1k
PRIVATE

Genomic tracks of structural variant breakpoints, copy number gains/amplifications or loss/deletions and SNV/Indels are shown.

Mullighan Lab

 
Approved - edits can only be made to update the visibility. Cannot change visibility after setting to public.
Whole Genome Sequencing
RNA Sequencing
ATAC Sequencing
HiChIP
hg38 / GRCh38
PASLPH CD1E::TAL1 Inversion
Oct 5, 2023
0
< 1k
PRIVATE

Depiction of H3K27ac HiChIP, H3K27ac coverage, diagnostic/germline sample WGS and WTS coverage in a T-ALL patient, showcasing enhancer hijacking of the CD1E enhancers by TAL1. The heatmap represent interactions between genomic loci, with color coding denoting...

Mullighan Lab

 
Approved - edits can only be made to update the visibility. Cannot change visibility after setting to public.
ChIP Sequencing
HiChIP
hg38 / GRCh38
Normal Healthy Controls
Oct 6, 2023
0
< 1k
PRIVATE

Healthy normal Double Positive (DP) and CD34+ HSPCs H3K27ac HiChIP (GSE165209) raw interactions as heatmaps, with corresponding H3K27ac coverage is shown. H3K27ac ChIPseq from different healthy thymic T-cells and in CD34+ cells is also shown from GSE151081.

Mullighan Lab

 
Approved - edits can only be made to update the visibility. Cannot change visibility after setting to public.
Whole Genome Sequencing
Whole Exome Sequencing
RNA Sequencing
hg38 / GRCh38
Oncoprint/Lollipop Plots of Recurrent Somatic SNV/indels
Oct 6, 2023
0
< 1k
PRIVATE

Explore the frequency-ordered heatmap depicting recurrent Single Nucleotide Variants (SNVs) and small Insertion/Deletions (Indels). To delve deeper into individual genes, click on their respective names within the heatmap to reveal detailed Lollipop plots.

Mullighan Lab

 
Approved - edits can only be made to update the visibility. Cannot change visibility after setting to public.
Whole Genome Sequencing
RNA Sequencing
HiChIP
hg38 / GRCh38
PAULRC BCL11B::HOXA13 Translocation
Oct 6, 2023
0
< 1k
PRIVATE

Depiction of H3K27ac HiChIP, H3K27ac Coverage, Diagnostic Sample, and Germline WGS/WTS Coverage in a T-ALL patient, showcasing enhancer hijacking of the BCL11B enhancers by HOXA13. The heatmap represent interactions between genomic loci, with color coding deno...

Mullighan Lab

 
Approved - edits can only be made to update the visibility. Cannot change visibility after setting to public.
Whole Genome Sequencing
RNA Sequencing
ATAC Sequencing
HiChIP
hg38 / GRCh38
PAVBLX BCL11B::LMO2 Translocation
Oct 6, 2023
0
< 1k
PRIVATE

Depiction of H3K27ac HiChIP, H3K27ac coverage, diagnostic/germline sample WGS and WTS coverage in a T-ALL patient, showcasing enhancer hijacking of the BCL11B enhancers by LMO2. The heatmap represent interactions between genomic loci, with color coding denotin...

Mullighan Lab

 
Approved - edits can only be made to update the visibility. Cannot change visibility after setting to public.
Whole Genome Sequencing
RNA Sequencing
ATAC Sequencing
HiChIP
hg38 / GRCh38
PAVCBR MIR181A1HG::HOXA13 Translocation
Oct 6, 2023
0
< 1k
PRIVATE

Depiction of H3K27ac HiChIP, H3K27ac coverage, diagnostic/germline sample WGS and WTS coverage in a T-ALL patient, showcasing enhancer hijacking of the MIR181A1HG enhancers by HOXA13. The heatmap represent interactions between genomic loci, with color coding d...

Mullighan Lab

 
Approved - edits can only be made to update the visibility. Cannot change visibility after setting to public.
Whole Genome Sequencing
RNA Sequencing
ATAC Sequencing
HiChIP
hg38 / GRCh38
PAVGMF MIR181A1HG::LMO2 Translocation
Oct 6, 2023
0
< 1k
PRIVATE

Depiction of H3K27ac HiChIP, H3K27ac coverage, diagnostic/germline sample WGS and WTS coverage in a T-ALL patient, showcasing enhancer hijacking of the MIR181A1HG enhancers by LMO2. The heatmap represent interactions between genomic loci, with color coding den...

Mullighan Lab

 
Approved - edits can only be made to update the visibility. Cannot change visibility after setting to public.
Whole Genome Sequencing
RNA Sequencing
ATAC Sequencing
HiChIP
hg38 / GRCh38
PAVPCZ MIR211HG::LMO2 Translocation
Oct 6, 2023
0
< 1k
PRIVATE

Depiction of H3K27ac HiChIP, H3K27ac coverage, diagnostic/germline sample WGS and WTS coverage in a T-ALL patient, showcasing enhancer generation by MIR211HG::LMO2 translocation. The heatmap represent interactions between genomic loci, with color coding denoti...

Mullighan Lab

 
Approved - edits can only be made to update the visibility. Cannot change visibility after setting to public.
Whole Genome Sequencing
RNA Sequencing
ATAC Sequencing
HiChIP
hg38 / GRCh38
PAUXAI TCRB::LMO3 Translocation
Oct 6, 2023
0
< 1k
PRIVATE

Depiction of H3K27ac HiChIP, H3K27ac coverage, diagnostic/germline sample WGS and WTS coverage in a T-ALL patient, showcasing enhancer hijacking of the TCRB enhancers by LMO3. The heatmap represent interactions between genomic loci, with color coding denoting...

Mullighan Lab

 
Approved - edits can only be made to update the visibility. Cannot change visibility after setting to public.
Whole Genome Sequencing
ATAC Sequencing
HiChIP
hg38 / GRCh38
PATEFF DHX9::TAL1 Inversion
Oct 6, 2023
0
< 1k
PRIVATE

Depiction of H3K27ac HiChIP, H3K27ac coverage, diagnostic/germline sample WGS and WTS coverage in a T-ALL patient, showcasing enhancer hijacking of the DHX9 enhancers by TAL1. The heatmap represent interactions between genomic loci, with color coding denoting...

Mullighan Lab

 
Approved - edits can only be made to update the visibility. Cannot change visibility after setting to public.
Whole Genome Sequencing
RNA Sequencing
ATAC Sequencing
HiChIP
hg38 / GRCh38
PAUJXZ TAL1 Enhancer Gain
Oct 6, 2023
0
< 1k
PRIVATE

Depiction of H3K27ac HiChIP, H3K27ac coverage, diagnostic/germline sample WGS and WTS coverage in a T-ALL patient, showcasing enhancer generation by enhancer gain downstream of TAL1. The heatmap represent interactions between genomic loci, with color coding de...

Mullighan Lab

 
Approved - edits can only be made to update the visibility. Cannot change visibility after setting to public.
Whole Genome Sequencing
RNA Sequencing
ATAC Sequencing
HiChIP
hg38 / GRCh38
PAUSNZ TCRB::HOXA13 Complex Rearrangement
Oct 6, 2023
0
< 1k
PRIVATE

Depiction of H3K27ac HiChIP, H3K27ac coverage, diagnostic/germline sample WGS and WTS coverage in a T-ALL patient, showcasing enhancer hijacking of the TCRB enhancers by HOXA13 through complex rearrangement. The heatmap represent interactions between genomic l...

Mullighan Lab

 
Approved - edits can only be made to update the visibility. Cannot change visibility after setting to public.
Whole Genome Sequencing
RNA Sequencing
ATAC Sequencing
HiChIP
hg38 / GRCh38
PAVHBC RAG::LMO2 Intergenic Loss
Oct 6, 2023
0
< 1k
PRIVATE

Depiction of H3K27ac HiChIP, H3K27ac coverage, diagnostic/germline sample WGS and WTS coverage in a T-ALL patient, showcasing enhancer hijacking of the RAG enhancers by LMO2. The heatmap represent interactions between genomic loci, with color coding denoting i...

Mullighan Lab

 
Approved - edits can only be made to update the visibility. Cannot change visibility after setting to public.
Whole Genome Sequencing
RNA Sequencing
ATAC Sequencing
HiChIP
hg38 / GRCh38
PAVIEN BCL11B::NKX2-1 Chromothripsis
Oct 6, 2023
0
< 1k
PRIVATE

Depiction of H3K27ac HiChIP, H3K27ac coverage, diagnostic/germline sample WGS and WTS coverage in a T-ALL patient, showcasing enhancer hijacking of the BCL11B enhancers by NKX2-1 after chromosome 14 chromothripsis. The heatmap represent interactions between ge...

Mullighan Lab

 
Approved - edits can only be made to update the visibility. Cannot change visibility after setting to public.
Whole Genome Sequencing
RNA Sequencing
ATAC Sequencing
HiChIP
hg38 / GRCh38
PAVLFA NFKBIA::NKX2-1 Intergenic Loss
Oct 6, 2023
0
< 1k
PRIVATE

Depiction of H3K27ac HiChIP, H3K27ac coverage, diagnostic/germline sample WGS and WTS coverage in a T-ALL patient, showcasing enhancer hijacking of the NFKBIA enhancers by NKX2-1. The heatmap represent interactions between genomic loci, with color coding denot...

Mullighan Lab

 
Approved - edits can only be made to update the visibility. Cannot change visibility after setting to public.
Whole Genome Sequencing
RNA Sequencing
ATAC Sequencing
HiChIP
hg38 / GRCh38
PAVZVG CELF1::LMO2 Intergenic Loss
Oct 6, 2023
0
< 1k
PRIVATE

Depiction of H3K27ac HiChIP, H3K27ac coverage, diagnostic/germline sample WGS and WTS coverage in a T-ALL patient, showcasing enhancer hijacking of the CELF1 enhancers by LMO2. The heatmap represent interactions between genomic loci, with color coding denoting...

Mullighan Lab

 
Approved - edits can only be made to update the visibility. Cannot change visibility after setting to public.
Whole Genome Sequencing
RNA Sequencing
ATAC Sequencing
HiChIP
hg38 / GRCh38
PAWGYX LMO2 Intronic Gain
Oct 6, 2023
0
< 1k
PRIVATE

Depiction of H3K27ac HiChIP, H3K27ac coverage, diagnostic/germline sample WGS and WTS coverage in a T-ALL patient, showcasing geomorphic promoter generation by small intronic gain at LMO2 loci. The heatmap represent interactions between genomic loci, with colo...

Mullighan Lab

 
Approved - edits can only be made to update the visibility. Cannot change visibility after setting to public.
Whole Genome Sequencing
RNA Sequencing
ATAC Sequencing
HiChIP
hg38 / GRCh38
PASPLG LMO2 Enhancer SNV/Indel
Oct 6, 2023
0
< 1k
PRIVATE

Depiction of H3K27ac HiChIP, H3K27ac coverage, diagnostic/germline sample WGS and WTS coverage in a T-ALL patient, showcasing enhancer generation by Enhancer SNV/Indel upstream of LMO2. The heatmap represent interactions between genomic loci, with color coding...

Mullighan Lab

 
Approved - edits can only be made to update the visibility. Cannot change visibility after setting to public.
Whole Genome Sequencing
RNA Sequencing
ATAC Sequencing
HiChIP
hg38 / GRCh38
PAUTJL TCRB::HOXA9 Inversion
Oct 6, 2023
0
< 1k
PRIVATE

Depiction of H3K27ac HiChIP, H3K27ac coverage, diagnostic/germline sample WGS and WTS coverage in a T-ALL patient, showcasing enhancer hijacking of the TCRB enhancers by HOXA9. The heatmap represent interactions between genomic loci, with color coding denoting...

Mullighan Lab

 
Approved - edits can only be made to update the visibility. Cannot change visibility after setting to public.
RNA Sequencing
hg38 / GRCh38
UMAP T-ALL Genetic Subtypes
Oct 11, 2023
0
< 1k
PRIVATE

UMAP scatterplot depicting T-ALL genetic subtypes. Key annotations are listed for each sample and can be seen by hovering over samples. UMAP can be subsetted based on various filters: Subtype, Driver Gene, TCR Rearrangement Classification, Leiden cluster lowr...

Mullighan Lab

 
Approved - edits can only be made to update the visibility. Cannot change visibility after setting to public.
RNA Sequencing
hg38 / GRCh38
UMAP: T-ALL Subtypes
Oct 11, 2023
0
< 1k
PRIVATE

UMAP scatterplot depicting T-ALL subtypes. Key annotations are listed for each sample and can be seen by hovering over samples. UMAP can be subsetted based on various filters: Subtype, Driver Gene, TCR Rearrangement Classification, Leiden cluster lowres annota...

Mullighan Lab