The Role of mutational processes in the evolution of somatic tissues and malignancy
Cells of our body are constantly exposed to events that can create lesions in the DNA. If unremoved by the DNA repair mechanisms, the lesion may lead to a mutational event. Some of these events might drive the transformation of a healthy cell to a malignant one. This thesis focuses on understanding...
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| Formato: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2021 |
| País: | España |
| Recursos: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/671532 |
| Acesso em linha: | http://hdl.handle.net/10803/671532 |
| Access Level: | acceso abierto |
| Palavra-chave: | Cancer Genomics Evolution Chemotherapy Mutational processes càncer Genòmica Evolució Quimioteràpia Processos mutacionals 576 |
| Resumo: | Cells of our body are constantly exposed to events that can create lesions in the DNA. If unremoved by the DNA repair mechanisms, the lesion may lead to a mutational event. Some of these events might drive the transformation of a healthy cell to a malignant one. This thesis focuses on understanding the generation of mutations and their positive selection in somatic tissues. First, we study the coding and noncoding driver landscape of more than 2500 patients. We also attempt to distinguish driver and passenger mutations in driver genes, and link them to mutational processes. We then study the mutations related to chemotherapies in both tumoral and healthy cells, as well as the effects of treatment in clonal hematopoiesis (CH). We also perform a systematic discovery of CH driver genes. Lastly, we study the interplay of DNA damage and repair in nucleosome-bound DNA, uncovering a 10bp periodic mutation rate which might have influenced the genome composition in eukarya. |
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