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in my independent group, i aim to study the crosstalk between genome and epigenome in cancer. my research project will primarily address the following questions: (1) determine the role of epigenetic remodeling in oncogenic transformation for tumors with recurrent copy number changes, and (2) investigate the consequences of somatic genomic alterations on the epigenetic landscape in cancer. the study aiming to answer the first question will be performed on neuroblastoma (nb) cells as this type of cancer exibits recurrent copy number alterations associated with poor prognosis. using chip-seq experiments, i am going to determine whether long range epigenetic silencing and, or activation exists in nb, whether epigenetic silencing can serve as an alternative mechanism to genomic aberrations, and detect potential tumor driver genes showing frequent patterns of epigenetic alteration. the study will be performed on nb cell lines (research funded by grant “enfants et santé”), followed by the analysis of nb primary tumors to study the association of epigenetic profiles with tumor aggressiveness. the second question aims to explore the interplay between large somatic structural variants and changes in the epigenetic landscape in cancer. i wish to link structural variants to the disruption of the architecture of lamina associated domains (lads) and topologically associating domains (tads). i want to prove that the disruption of these domains by structural variants is one of the important mechanisms utilized by cancer to change the expression of cancer driver genes. for the analysis, i will use gene expression, copy number and structural variant datasets coming from more than 2000 samples of twelve cancer types (data access is granted by the pan-cancer wgs project). the validation experiments will be performed in collaboration with the bas van steensel lab (nki, netherlands).