An Expressed Retrogene of the Master Embryonic Stem Cell Gene POU5F1 Is Associated with Prostate Cancer Susceptibility

摘要

Genetic association studies ofeprostate and other cancers have identified a major risk locus at chromosome 8q24. Several independent risk variants at this locus alter transcriptional regulatory elements, but an affected gene and mechanism for cancer predisposition have remained elusive. The retrogene P0U5F1B within the locus has a preserved open reading frame encoding a homolog of the master embryonic stem cell transcription factor Oct4. We find that 8q24 risk alleles are expression quantitative trait loci correlated with reduced expression of POU5F1B in prostate tissue and that predicted deleterious POUSF1B missense variants are also associated with risk of transformation. P0U5F1 is known to be self-regulated by the encoded Oct4 transcription factor. We further observe that P0U5F1 expression is directly correlated with POUSF1B expression. Our results suggest that a pathway critical to self-renewal of embryonic stem cells may also have a role in the origin of cancer.