The cellular origin of cancer

The importance of the cell-of-origin to tumor development. A. Genetic view of normal versus tumor comparison. B and C. Normal cells are characterized by tissue-specific epigenomes that are further influenced by genetic, developmental stage, age or environmental stimuli.

The detailed molecular mechanisms that lead to epigenetic changes in the tumor genome are not understood. This is, however, of upmost importance if one considers the development of novel therapies. We have ongoing research projects that will allow us to decipher the epigenome (DNA methylation, nucleosome position and histone marks) of cells identified as potential tumor origin and in comparison with the tumor epigenome, will identify cancer-specific epigenetic changes. This information is of upmost importance in order to understand the epigenomic contributions in a cancer cell to development and progression of tumorigenesis, as well as to therapy response. We utilize unique existing resources and expertise (tissues resources, cell biology assays, epigenetic profiling protocols, bioinformatical analysis pipelines, and clinical/pathology resources). Based on our current knowledge, we work on the following hypothesis: The epigenome of cancer cells is highly variable and reflects patterns preexisting in the cell-of-origin in addition to cancer-specific events.


Oakes CC, Seifert M, Assenov Y, Gu L, Przekopowitz M, Ruppert AS, Wang Q, Serva A, Koser S, Brocks D, Lipka D, Bogatyrova O, Mertens D, Zapatka M, Lichter P, Döhner H, Küppers R, Zenz T, Stilgenbauer S, Byrd JC and Plass C. Progressive epigenetic programming during B cell maturation yields a continuum of disease phenotypes in chronic lymphocytic leukemia. Nat Genet 48(3): 253-64, 2016.

Wierzbinska JA, Toth R, Ishaque N, Rippe K, Mallm JP, Klett LC, Mertens D, Zenz T, Hielscher T, Seifert M, Küppers R, Assenov Y, Lutsik P, Stilgenbauer S, Roessner PM, Seiffert M, Byrd J, Oakes CC, Plass C, Lipka DB. Methylome-based cell-of-origin modeling (Methyl-COOM) identifies aberrant expression of immune regulatory molecules in CLL. Genome Med. 12(1): 29, 2020.

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