DR-247 A comprehensive analysis of mutational processes and signatures in primary and metastatic cancer tumors

Tumor metastasis involves dissemination of cancer cells of primary tumors to distant organ sites. Though current cancer research has delineated important mutation features in primary cancer tumors, the identification and understanding of the genetic and genomic profiles is less complete in metastatic cancer. Therefore, understanding the genomic differences between primary untreated and late-stage treated metastatic tumors is essential to understand the cancer evolution and to address potential therapeutic vulnerabilities. In this study, we will perform the largest harmonised analysis (i.e. processed through the same analytical pipeline) of primary tumors (N=2500) from PCWAG and metastatic samples (N=5000) from the Hartwig dataset. The results of this study will provide a better understanding of the processes that are operational at different stages of carcinogenesis. Such information may be used for design of preventive strategies (for tumorgenesis or metastatic seeding) but can also be used for stratifying patients towards targeted treatments based on such characterics (e.g. homologous recombination deficiency as we have already demonstrated by development of the CHORD algorithm, DR-018).

Arne van Hoeck, Universtair Medisch Centrum Utrecht (UMCU), the Netherlands