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| Status |
Public on Mar 03, 2022 |
| Title |
Acute lymphoblastic leukemia displays a distinct highly methylated genome |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
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| Summary |
DNA methylation is tightly regulated during development and is stably maintained in normal cells. In contrast, the methylome of cancer cells is commonly characterized by a global loss of DNA methylation co-occurring with CpG island hypermethylation. In acute lymphoblastic leukemia (ALL), the commonest childhood cancer, perturbations of CpG methylation have been reported to be associated with genetic disease subtype and outcome, but data examining large cohorts at genome-wide scale are lacking. Here, we performed whole-genome bisulfite sequencing of leukemic cells across multiple subtypes of ALL, leukemia cell lines and normal hematopoietic cells, and show that in contrast to most cancers, ALL samples only exhibit CpG island hypermethylation but minimal global loss of methylation. This was most pronounced in T-ALL and accompanied by an exceptionally broad range of hypermethylation of CpG islands between patients that is influenced by TET2 and DNMT3B. These findings demonstrate that ALL is characterized by an unusually highly methylated genome, and provide insights into the deregulation of methylation in cancer.
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| Overall design |
Genome-wide DNA methylation profiling of B-ALL and T-ALL cell lines as well as DNA methylation and expression profiling of Jurkat cells with TET2 knockout.
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| Contributor(s) |
Hetzel S, Mattei AL, Kretzmer H, Qu C, Chen X, Fan Y, Wu G, Roberts KG, Luger S, Litzow M, Rowe J, Paietta E, Stock W, Mardis ER, Wilson RK, Downing JR, Mullighan CG, Meissner A |
| Citation(s) |
35590059 |
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| Submission date |
Dec 30, 2020 |
| Last update date |
May 27, 2022 |
| Contact name |
Sara Hetzel |
| E-mail(s) |
hetzel@molgen.mpg.de
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| Organization name |
Max Planck Institute for Molecular Genetics
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| Department |
Genome Regulation
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| Lab |
Meissner Lab
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| Street address |
Ihnestraße 63
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| City |
Berlin |
| ZIP/Postal code |
14195 |
| Country |
Germany |
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| Platforms (2) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (25)
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| Relations |
| BioProject |
PRJNA688699 |
| SRA |
SRP299802 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE164040_RAW.tar |
2.7 Gb |
(http)(custom) |
TAR (of BED, TAB, TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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