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| Home > Publications database > Methylome-based cell-of-origin modeling (Methyl-COOM) identifies aberrant expression of immune regulatory molecules in CLL. > print |
| Home > Publications database > Methylome-based cell-of-origin modeling (Methyl-COOM) identifies aberrant expression of immune regulatory molecules in CLL. > print |
| 001 | 154170 | ||
| 005 | 20240229123057.0 | ||
| 024 | 7 | _ | |a 10.1186/s13073-020-00724-7 |2 doi |
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| 100 | 1 | _ | |a Wierzbinska, Justyna Anna |0 P:(DE-He78)fd7de20653a8cbc8aee25717fa667280 |b 0 |e First author |
| 245 | _ | _ | |a Methylome-based cell-of-origin modeling (Methyl-COOM) identifies aberrant expression of immune regulatory molecules in CLL. |
| 260 | _ | _ | |a London |c 2020 |b BioMed Central |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1630396268_30128 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
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| 520 | _ | _ | |a In cancer, normal epigenetic patterns are disturbed and contribute to gene expression changes, disease onset, and progression. The cancer epigenome is composed of the epigenetic patterns present in the tumor-initiating cell at the time of transformation, and the tumor-specific epigenetic alterations that are acquired during tumor initiation and progression. The precise dissection of these two components of the tumor epigenome will facilitate a better understanding of the biological mechanisms underlying malignant transformation. Chronic lymphocytic leukemia (CLL) originates from differentiating B cells, which undergo extensive epigenetic programming. This poses the challenge to precisely determine the epigenomic ground state of the cell-of-origin in order to identify CLL-specific epigenetic aberrations.We developed a linear regression model, methylome-based cell-of-origin modeling (Methyl-COOM), to map the cell-of-origin for individual CLL patients based on the continuum of epigenomic changes during normal B cell differentiation.Methyl-COOM accurately maps the cell-of-origin of CLL and identifies CLL-specific aberrant DNA methylation events that are not confounded by physiologic epigenetic B cell programming. Furthermore, Methyl-COOM unmasks abnormal action of transcription factors, altered super-enhancer activities, and aberrant transcript expression in CLL. Among the aberrantly regulated transcripts were many genes that have previously been implicated in T cell biology. Flow cytometry analysis of these markers confirmed their aberrant expression on malignant B cells at the protein level.Methyl-COOM analysis of CLL identified disease-specific aberrant gene regulation. The aberrantly expressed genes identified in this study might play a role in immune-evasion in CLL and might serve as novel targets for immunotherapy approaches. In summary, we propose a novel framework for in silico modeling of reference DNA methylomes and for the identification of cancer-specific epigenetic changes, a concept that can be broadly applied to other human malignancies. |
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| 700 | 1 | _ | |a Rippe, Karsten |0 P:(DE-He78)94de5f7413279464b6e738d91dfae1eb |b 3 |
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| 700 | 1 | _ | |a Klett, Lara C |0 P:(DE-He78)dd57fd8197d9c5e0290f104db294e019 |b 5 |
| 700 | 1 | _ | |a Mertens, Daniel |0 P:(DE-He78)833c06a995d272b78f3a20df3eba6e9e |b 6 |
| 700 | 1 | _ | |a Zenz, Thorsten |0 P:(DE-He78)f3d5f16b49eb47520def635be98d5576 |b 7 |
| 700 | 1 | _ | |a Hielscher, Thomas |0 P:(DE-He78)743a4a82daab55306a2c88b9f6bf8c2f |b 8 |
| 700 | 1 | _ | |a Seifert, Marc |b 9 |
| 700 | 1 | _ | |a Küppers, Ralf |b 10 |
| 700 | 1 | _ | |a Assenov, Yassen |0 P:(DE-He78)45a6854ecf41ba2e65ca3ba0d560f14c |b 11 |
| 700 | 1 | _ | |a Lutsik, Pavlo |0 P:(DE-He78)ff1677c63392be9b31a1c8d23db7c9dc |b 12 |
| 700 | 1 | _ | |a Stilgenbauer, Stephan |b 13 |
| 700 | 1 | _ | |a Roessner, Philipp M |0 P:(DE-HGF)0 |b 14 |
| 700 | 1 | _ | |a Seiffert, Martina |0 P:(DE-He78)e67f907703fcb2cf909f4d72d50268b5 |b 15 |
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| 700 | 1 | _ | |a Oakes, Christopher C |b 17 |
| 700 | 1 | _ | |a Plass, Christoph |0 P:(DE-He78)4301875630bc997edf491c694ae1f8a9 |b 18 |e Last author |
| 700 | 1 | _ | |a Lipka, Daniel |0 P:(DE-He78)c403a040c97f91902a7d31b93859f9fc |b 19 |e Last author |
| 773 | _ | _ | |a 10.1186/s13073-020-00724-7 |g Vol. 12, no. 1, p. 29 |0 PERI:(DE-600)2484394-5 |n 1 |p 29 |t Genome medicine |v 12 |y 2020 |x 1756-994X |
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