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...
| Author: | |
|---|---|
| Format: | Doctoral thesis |
| Status: | Published version |
| Publication date: | 2021 |
| Country: | España |
| Institution: | CBUC, CESCA |
| Repository: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/671532 |
| Online Access: | http://hdl.handle.net/10803/671532 |
| Access Level: | Open access |
| Keyword: | Cancer Genomics Evolution Chemotherapy Mutational processes càncer Genòmica Evolució Quimioteràpia Processos mutacionals 576 |
| _version_ | 1878741304104452096 |
|---|---|
| author | Pich Roselló, Oriol |
| author_browse | Pich Roselló, Oriol |
| author_facet | Pich Roselló, Oriol |
| author_role | author |
| collection | TDR. Tesis Doctorales en Red |
| description | 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. |
| eu_rights_str_mv | openAccess |
| format | doctoralThesis |
| id | ES_e2d2f9acdbee81c2abefd7c65d1d5d2e |
| institution | CBUC, CESCA |
| instname_str | CBUC, CESCA |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:www.tdx.cat:10803/671532 |
| publishDate | 2021 |
| publishDateSort | 2021 |
| reponame_str | TDR. Tesis Doctorales en Red |
| spelling | The Role of mutational processes in the evolution of somatic tissues and malignancy Pich Roselló, Oriol Cancer Genomics Evolution Chemotherapy Mutational processes càncer Genòmica Evolució Quimioteràpia Processos mutacionals 576 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. Les cèl·lules del nostre cos estan constantment exposades a esdeveniments que poden lesionar l’ADN. Si aquestes lesions no són eliminades pels mecanismes de reparació, poden causar mutacions. Alguns d’aquests podrien ajudar a transformar una cèl·lula sana en una maligna. Aquesta tesi doctoral té com objectiu estudiar la generació de les mutacions i com són seleccionades positivament als teixits somàtics. Primer, estudiem el panorama de drivers en zones codificant i no codificant en més de 2500 pacients. També intentem distingir quines mutacions són driver de les passenger, i les relacionem amb els processos mutacionals. Després estudiem les mutacions relacionades amb la quimioteràpia en cèl·lules sanes i tumorals, i també l’efecte que tenen a la hematopoesi clonal. D’aquest últim fenomen en descobrim els gens drivers. Per últim, estudiem la relació entre el dany a l’ADN i els mecanismes de reparació quan la molècula s’empaqueta en nucleosomes. Aquesta relació deixa una periodicitat de 10 parells de bases que pot haver influenciat la composició del genoma dels eucariotes. Programa de doctorat en Biomedicina http://hdl.handle.net/10803/671532 |
| spellingShingle | The Role of mutational processes in the evolution of somatic tissues and malignancy Pich Roselló, Oriol Cancer Genomics Evolution Chemotherapy Mutational processes càncer Genòmica Evolució Quimioteràpia Processos mutacionals 576 |
| status_str | publishedVersion |
| title | The Role of mutational processes in the evolution of somatic tissues and malignancy |
| title_full | The Role of mutational processes in the evolution of somatic tissues and malignancy |
| title_fullStr | The Role of mutational processes in the evolution of somatic tissues and malignancy |
| title_full_unstemmed | The Role of mutational processes in the evolution of somatic tissues and malignancy |
| title_short | The Role of mutational processes in the evolution of somatic tissues and malignancy |
| title_sort | The Role of mutational processes in the evolution of somatic tissues and malignancy |
| topic | Cancer Genomics Evolution Chemotherapy Mutational processes càncer Genòmica Evolució Quimioteràpia Processos mutacionals 576 |
| topic_facet | Cancer Genomics Evolution Chemotherapy Mutational processes càncer Genòmica Evolució Quimioteràpia Processos mutacionals 576 |
| url | http://hdl.handle.net/10803/671532 |