Exploration of oncogenic cooperation between germline variation and somatic mutation in progression of prostate cancer

While recent advances in omics technologies have provided clues as to how molecular changes shape the onset and progression of PCa, it remains unclear whether germline variants and somatic mutations cooperate to contribute to PCa progression and outcome. Thus, we explored whether oncogenic cooperation between regulatory germline variants and somatic driver mutations may help explain why some PCa patients develop a more aggressive phenotype, which may have implications for risk-adapted medical treatment.

We discovered PTPRK receptor-type protein-tyrosine phosphatase kappa (PTPRK) as a TMPRSS2::ERG (TE)-modulated gene associated with PCa progression whose expression is controlled by cooperation of the TE-fusion with a regulatory single nucleotide polymorphism (SNP).