Claudia Serrano Colome

Abstract Mutations drive evolution and genetic diversity, but the impact of transcription on germline mutagenesis remains poorly understood. Here, we identify a hypermutation phenomenon at transcription start sites in the human germline, spanning several hundred base pairs in both directions.

Abstract Cancer is an evolutionary disease driven by mutations in asexually-reproducing somatic cells. In asexual microbes, bias reversals in the mutation spectrum can speed adaptation by increasing access to previously undersampled beneficial mutations. By analyzing tumors from 20 tissues, along with normal tissue and the germline, we demonstrate this effect in cancer. Non-hypermutated tumors reverse the germline mutation bias and have consistent spectra across tissues.

Abstract DNA mutational processes generate patterns of somatic and germline mutations. A multitude of such mutational processes has been identified and linked to biochemical mechanisms of DNA damage and repair. Cancer genomics relies on these so-called mutational signatures to classify tumours into subtypes, navigate treatment, deter- mine exposure to mutagens, and characterise the origin of individual mutations.