What is REPAIRSCAPE? "The genomic landscape of mutagenesis resulting from DNA repair failures in human tumors (REPAIRSCAPE)" is a research project funded by the Spanish government (MICINN, the Ministry of Science and Innovation).

The PI is Fran Supek, the project lasts 3 years (2021-2024), and is funded by approximately 270k € (including the attached FPI student position).

What is the major impact of the project? The REPAIRSCAPE project will elucidate the rules underlying genomic instability due to common DNA repair deficiencies in human cells, by examining novel types of genomic mutational patterns. Our work will have (i) a major technical impact on developing novel statistical methodology for analysis of mutation patterns, and will have a (ii) a major scientific impact in furthering our understanding of cancer evolution and also (iii) shedding light on potential therapeutic implications.

What is the broader significance of REPAIRSCAPE? Cancer aside, learning about mutability is also more broadly relevant to studies of other genetic disorders (which often stem from de novo or evolutionarily recent mutations in the germline) and more generally to studies of human evolution, where understanding the rules of mutation supply will elucidate the diversity of genetic variants in human populations. Finally, it is well plausible that aging and age-related disorders could be affected by somatic mutation. Therefore, characterizing the mutational processes in healthy cells will add towards our current knowledge on how the genome of human cells deteriorates with age.

There is a strong need for personalizing the recurrent and toxic cancer therapies to minimize side-effects and cost, and to maximize patient benefit. We envision that future work building upon REPAIRSCAPE project may provide novel genetic markers for stratifying cancer patients to receive chemotherapies (e.g. ATRi, PARPi) and/or immunotherapies. Additionally, methodologies that we will develop in this project may inform future genomics-based strategies to prevent drug resistance.