The Impact of germline variants on human somatic mutation processes
Somatic mutations are an inevitable component of ageing and the most important cause of cancer. The rates and types of somatic mutation vary across individuals, but relatively few inherited influences on mutation processes are known. Here, we performed systematic studies investigating the influence...
| Autor: | |
|---|---|
| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/674462 |
| Acceso en línea: | http://hdl.handle.net/10803/674462 |
| Access Level: | acceso abierto |
| Palabra clave: | Cancer Genomics Mutacional processes Gemline variants Heritability of cancer Càncer Genòmica Processos mutacionals Variants de la línia germinal Heretabilitat del càncer 575 |
| Sumario: | Somatic mutations are an inevitable component of ageing and the most important cause of cancer. The rates and types of somatic mutation vary across individuals, but relatively few inherited influences on mutation processes are known. Here, we performed systematic studies investigating the influence of rare and common germline variants on somatic mutational processes. Firstly, we extracted somatic mutational components via independent component analysis and variational autoencoder neural networks from human cancer genomes. Secondly, we identified via a gene-based rare damaging variant association study with diverse mutational processes that diverse genes associate with many different mutational processes. Thirdly, in a genome-wide association study between common germline variants and different mutational processes, several hits at genome-wide significance were identified. Fourthly, significant heritable somatic mutational processes based on common variants were detected and heritability of the total mutation burden could be attributed to at least three different mutational processes. Overall, we suggest that mutational processes in our cells have an important heritable component, contributing to inter-individual differences in somatic mutation accumulation. |
|---|