|
| Status |
Public on May 01, 2020 |
| Title |
Comparative analysis of genome-wide DNA methylation identifies patterns that associate with conserved transcriptional programs in osteosarcoma |
| Organisms |
Homo sapiens; Canis lupus familiaris |
| Experiment type |
Methylation profiling by high throughput sequencing
|
| Summary |
Osteosarcoma is an aggressive tumor of the bone that primarily affects young adults and adolescents. Osteosarcoma is characterized by genomic chaos and heterogeneity. While inactivation of tumor suppressor p53 TP53 is nearly universal other high frequency mutations or structural variations have not been identified. Despite this genomic heterogeneity, key conserved transcriptional programs associated with survival have been identified across human, canine and induced murine osteosarcoma. The epigenomic landscape, including DNA methylation, plays a key role in establishing transcriptional programs in all cell types. The role of epigenetic dysregulation has been studied in a variety of cancers but has yet to be explored at scale in osteosarcoma. Here we examined genome-wide DNA methylation patterns in 24 human and 44 canine osteosarcoma samples identifying groups of highly correlated DNA methylation marks in human and canine osteosarcoma samples. We also link specific DNA methylation patterns to key transcriptional programs in both human and canine osteosarcoma. Building on previous work, we built a DNA methylation-based measure for the presence and abundance of various immune cell types in osteosarcoma. Finally, we determined that the underlying state of the tumor, and not changes in cell composition, were the main driver of differences in DNA methylation across the human and canine samples. Significance: This is the first large scale study of DNA methylation in osteosarcoma and lays the ground work for the exploration of DNA methylation programs that help establish conserved transcriptional programs in the context of different genomic landscapes.
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| |
|
| Overall design |
Targeted whole genome bisulfite sequencing of primary osteosarcoma tumors
|
| |
|
| Contributor(s) |
Mills L, Modiano J |
| Citation(s) |
33127576 |
| |
| Submission date |
Apr 30, 2020 |
| Last update date |
Feb 27, 2023 |
| Contact name |
Lauren Mills |
| E-mail(s) |
ljmills@umn.edu
|
| Phone |
6126241540
|
| Organization name |
University of Minnesota
|
| Department |
Department of Pediatrics
|
| Street address |
420 Delaware St SE
|
| City |
Minneapolis |
| State/province |
MN |
| ZIP/Postal code |
55455 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL16540 |
Illumina HiSeq 2000 (Canis lupus familiaris) |
|
| Samples (68)
|
|
| Relations |
| BioProject |
PRJNA629591 |
| SRA |
SRP259904 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE149679_130912_HG19_CpGiant_4M_EPI.bed.gz |
1.8 Mb |
(ftp)(http) |
BED |
| GSE149679_150825_CanFam_methylome_EPI_primary_targets.bed.gz |
1.9 Mb |
(ftp)(http) |
BED |
| GSE149679_blueprint_downloads.xlsx |
10.9 Kb |
(ftp)(http) |
XLSX |
| GSE149679_canine_MethValues_allSamples_crossSpecies.txt.gz |
4.9 Mb |
(ftp)(http) |
TXT |
| GSE149679_canine_moduleMembers_crossSpecies.xlsx |
309.7 Kb |
(ftp)(http) |
XLSX |
| GSE149679_canine_module_pathway_crossSpecies.xlsx |
23.1 Kb |
(ftp)(http) |
XLSX |
| GSE149679_canine_numberMembers_byModule.xlsx |
8.4 Kb |
(ftp)(http) |
XLSX |
| GSE149679_diffMeth_regions_pureCellPop.xlsx |
126.4 Kb |
(ftp)(http) |
XLSX |
| GSE149679_dogMeth_hg38coord_closest_humanMeth_hg38coord.txt.gz |
2.2 Mb |
(ftp)(http) |
TXT |
| GSE149679_human_MethValues_allSamples_crossSpecies.txt.gz |
3.4 Mb |
(ftp)(http) |
TXT |
| GSE149679_human_moduleMembership_crossSpecies.xlsx |
771.1 Kb |
(ftp)(http) |
XLSX |
| GSE149679_human_module_pathway_crossSpecies.xlsx |
60.3 Kb |
(ftp)(http) |
XLSX |
| GSE149679_human_numberMembers_byModule.xlsx |
9.1 Kb |
(ftp)(http) |
XLSX |
| GSE149679_sorted_130912_HG19_CpGiant_4M_EPI_windowed.bed.gz |
2.9 Mb |
(ftp)(http) |
BED |
| GSE149679_sorted_150825_CanFam_methylome_EPI_primary_targets_windowed.bed.gz |
1.7 Mb |
(ftp)(http) |
BED |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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