Periodic Reporting for period 3 - NONCODRIVERS (Finding noncoding cancer drivers)
Reporting period: 2019-12-01 to 2021-05-31
Most of the work on cancer research have been focused in the study of the coding genome, which comprise less than 2% of the genome sequence. This has allowed us to identify several hundreds of genes involved in tumorigenesis through mutations that affect their coding sequence. On the other hand, only a handful of non-coding driver elements have been identified to date. Our project aims to study what is the role of somatic mutations in the non-coding genome in cancer development.
We have also collected data from thousands of tumor whole-genomes from different sources.
As part of the analysis of mutations in non-coding regions we have discovered that the rate at which mutations accumulate in different regions of the genome is highly variable at the local level. We have advanced significantly in understanding the reasons of these variability in terms of accumulation of DNA damage and the activity of DNA repair along the genome. These are important basic biology results and are also important to accurately identify of cancer driver mutations.
We will improve the computational methodologies to identify cancer driver mutations by incorporating the knowledge obtained about the local variability on the accumulation of mutations in the calculation of the background mutation rate.
We continue the analyses of tumor whole-genomes with the newly collected tumor whole-genomes and the new methods.
We will validate functionally the most promising novel candidate non-coding cancer driver mutations.