PCFENCM · Pan-cancer functional evaluation of non-coding DNA mutations

Pan-cancer functional evaluation of non-coding DNA mutations

Cancer is a genetic disease that arises from the accumulation of somatic alterations (mutations) in the DNA of the cells. Somatic mutations in human cancers come in many ways, from base substitutions to the loss or duplication of entire chromosomes. The advent of Next Generation Sequencing (NGS) over the last decade has permitted the analysis of human cancers at an unprecedented resolution. Traditionally, studies of cancer mutations have focused on the analysis of protein-coding mutations using Sanger, targeted or exome sequencing (that is, the analysis of mutations in genes). Although the study of mutations in genes using these sequencing modalities, especially those in cancer-related and tumor suppressors, provide a great amount of information to guide therapeutic intervention and to characterize the mutational processes operative in cancer cells, such approaches do not permit to study the non-coding genome (~98% of the genome), whose relevance for disease (not only cancer) is becoming more and more apparent. Moreover, these technologies do not permit the study of the large structural alterations of the genome, which are a hallmark of cancer, at base resolution. This is due to the fact that structural alterations often map to the non-coding genome. The analysis of the entire genome of cancer cells using whole-genome sequencing (WGS) has been hampered by technical limitations, data analysis limitations and sequencing cost. Today, given the decrease in sequencing costs and the increase in computational power and data storage capabilities cloud-computing capabilities, whole-genome sequencing of large collections of tumors has become feasible. The overall goal of this project is to study genomic rearrangements in human cancers on a genome-wide basis using whole-genome sequencing. Whole-genome analysis of tumors will enable the characterization of the large-scale mutational processes operative in human tumors and establish their role in cancer progression. Finally, interrogating the entire genome of human tumors will also permit to assess the relevance and practical usefulness of whole-genome sequencing for biomarker discovery and cancer subtype diagnosis in clinical settings.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз