PhD defence J.(Job) van Riet

Dissertation in short:

The use of Next-Generation Sequencing, and in particular whole-genome sequencing, has allowed researchers an unbiased look at the genetic landscape underlying cancer. Within this thesis, we have developed new applications to take advantage of this wealth of information such as SNPitty and ProteoDisco and we have generated in-depth whole-genome mutational overviews of large cohorts of metastatic prostate cancer and locally-advanced neuro-endocrine cancer. Among others, we showed the potential of stratifying prostate cancer based on underlying genomic characteristics for patient-specific therapies, identified upstream enhancers of AR and MYC within non-coding regions within prostate cancer and were able to uniformly describe the enigmatic nature of neuro-endocrine malignancies. Furthermore, we reveal a potential new subgroup of primary prostate cancers, constituting ~25% of total cases, which makes heavy use of the potent immune-regulatory kynurine pathway (though TDO2) to establish a favorable tumor micro-environment.