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with Prof. Joachim Weischenfeldt
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Date : Thursday November 9th – 12h15
Location : Auditoire A – Génopode
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"Mutational processes shaping structural variants in cancer genomes"
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The mutations observed in cancer genomes are influenced by intrinsic and extrinsic mutational processes and evolutionary selection. This is particularly true for Structural variants (SVs), which affect larger parts of the cancer genome than any other type of somatic alterations. SVs include aneuploidies and rearrangements of the genome that can span up to megabases in size. SVs can manifest as simple events such as deletions, duplications, and translocations, as well as more complex events such as chromothripsis or breakage fusion bridge cycles. Understanding what drives the formation of simple and complex SVs has been challenging due to their lower site-recurrence compared to point mutations.
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We have found a strong influence of 3D genome architecture in driving the formation and consequences of SVs in cancer genomes. By leveraging well-defined human model systems and large-scale patient-tumor material, we show that the prior 3D genome architecture impacts where and which types of SVs are formed, including the formation of complex SVs that bridge two or several chromosomes. We also demonstrate that SVs can have a strong and long-range influence on the local 3D genome topology and can affect transcriptional regulation at a distance.
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