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| Status |
Public on Jan 23, 2016 |
| Title |
Activation of proto-oncogenes by disruption of chromosome neighborhoods [5C-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
Mutations such as gene fusion, translocation and focal amplification are a frequent cause of proto-oncogene activation during tumorigenesis, but such mutations do not explain all cases of proto-oncogene activation. Here we show that disruption of local chromosome conformation can also activate proto-oncogenes in human cells. We mapped chromosome structures in T-cell acute lymphoblastic leukemia (T-ALL), and found that active oncogenes and silent proto-oncogenes generally occur within insulated neighborhoods formed by the looping of two interacting CTCF sites co-occupied by cohesin. Recurrent microdeletions frequently overlap neighborhood boundary sites in T-ALL genomes, and we demonstrate that site-specific perturbation of loop boundaries is sufficient to activate the respective proto-oncogenes in non-malignant cells. We found somatic genomic rearrangements affecting loop boundaries in many cancers. These results suggest that chromosome structural organization is fundamental to identify functional somatic alterations in cancer genomes.
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| Overall design |
5C analysis of Tal1 and LMO2 in wildtype and mutant HEK293T cells
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| Contributor(s) |
Hnisz D, Weintraub AS, Day DS, Valton A, Bak RO, Li CH, Goldmann J, Lajoie BR, Fan ZP, Sigova AA, Reddy J, Borges-Rivera D, Lee TI, Jaenisch R, Porteus MH, Dekker J, Young RA |
| Citation(s) |
26940867 |
| Submission date |
Jan 22, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Richard A Young |
| E-mail(s) |
young_computation@wi.mit.edu
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| Phone |
617-258-5219
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| Organization name |
Whitehead Institute for Biomedical Research
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| Lab |
Young Lab
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| Street address |
9 Cambridge Center
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| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02142 |
| Country |
USA |
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| Platforms (2) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL15520 |
Illumina MiSeq (Homo sapiens) |
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| Samples (9)
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| This SubSeries is part of SuperSeries: |
| GSE68978 |
Activation of proto-oncogenes by disruption of chromosome neighborhoods |
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| Relations |
| BioProject |
PRJNA309545 |
| SRA |
SRP068783 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE77142_8611_5CYoung-HEK239T-Lmo2Del-R2.matrix.gz |
353.7 Kb |
(ftp)(http) |
MATRIX |
| GSE77142_8612_5CYoung-HEK239T-Tal1Del-R2.matrix.gz |
371.8 Kb |
(ftp)(http) |
MATRIX |
| GSE77142_8613_5CYoung-HEK239T-WT-R2.matrix.gz |
367.0 Kb |
(ftp)(http) |
MATRIX |
| GSE77142_8614_5CYoung-HEK239T-Lmo2Del.matrix.gz |
431.3 Kb |
(ftp)(http) |
MATRIX |
| GSE77142_8614_5CYoung-HEK239T-Lmo2Del_20000_8_6343_2MbHindIIITal1_cis.matrix.gz |
667.6 Kb |
(ftp)(http) |
MATRIX |
| GSE77142_8614_5CYoung-HEK239T-Lmo2Del_20000_8_6344_2MbHindIIILmo2_cis.matrix.gz |
867.3 Kb |
(ftp)(http) |
MATRIX |
| GSE77142_8615_5CYoung-HEK239T-Tal1Del.matrix.gz |
444.7 Kb |
(ftp)(http) |
MATRIX |
| GSE77142_8615_5CYoung-HEK239T-Tal1Del_20000_8_6343_2MbHindIIITal1_cis.matrix.gz |
668.0 Kb |
(ftp)(http) |
MATRIX |
| GSE77142_8615_5CYoung-HEK239T-Tal1Del_20000_8_6344_2MbHindIIILmo2_cis.matrix.gz |
886.5 Kb |
(ftp)(http) |
MATRIX |
| GSE77142_8616_5CYoung-HEK239T-WT.matrix.gz |
438.2 Kb |
(ftp)(http) |
MATRIX |
| GSE77142_8616_5CYoung-HEK239T-WT_20000_8_6343_2MbHindIIITal1_cis.matrix.gz |
669.1 Kb |
(ftp)(http) |
MATRIX |
| GSE77142_8616_5CYoung-HEK239T-WT_20000_8_6344_2MbHindIIILmo2_cis.matrix.gz |
883.9 Kb |
(ftp)(http) |
MATRIX |
| GSE77142_8617_5CYoung-HEK239T-Lmo2Del-R1.matrix.gz |
390.6 Kb |
(ftp)(http) |
MATRIX |
| GSE77142_8618_5CYoung-HEK239T-Tal1Del-R1.matrix.gz |
400.5 Kb |
(ftp)(http) |
MATRIX |
| GSE77142_8619_5CYoung-HEK239T-WT-R1.matrix.gz |
390.6 Kb |
(ftp)(http) |
MATRIX |
| GSE77142_distance-adjusted_LMO2_Lmo2Del_WT.subtract.matrix.gz |
941.6 Kb |
(ftp)(http) |
MATRIX |
| GSE77142_distance-adjusted_LMO2_Tal1Del_WT.subtract.matrix.gz |
944.4 Kb |
(ftp)(http) |
MATRIX |
| GSE77142_distance-adjusted_TAL1_Lmo2Del_WT.subtract.matrix.gz |
728.4 Kb |
(ftp)(http) |
MATRIX |
| GSE77142_distance-adjusted_TAL1_Tal1Del_WT.subtract.matrix.gz |
730.1 Kb |
(ftp)(http) |
MATRIX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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