Abstract
Abstract Genetic association studies of prostate and other cancers have identified a major risk locus at chromosome 8q24, but a causal gene and a mechanism for cancer predisposition has remained elusive. The locus harbors the POU5F1B retrogene and several non-coding RNA genes, and is also proximal to the MYC oncogene. The open reading frame of the retrogene is preserved with 96% identity to that of the parent POU5F1 gene on chromosome 6, encoding the master embryonic stem cell factor Oct4. We observed that 8q24 risk alleles are significantly correlated with reduced expression of the POU5F1B retrogene in normal prostate tissue. The alleles were not correlated with the expression of MYC or other flanking genes in normal prostate tissue. Predicted deleterious POU5F1B missense germline variants were also associated with risk of prostate cancer. Thus, two independent lines of genetic evidence support a potential causal role for POU5F1B in the transformation of normal prostate tissue. A plausible hypothesis of POU5F1B function is dysregulation of Oct4; POU5F1 is transcriptionally regulated by the encoded Oct4 transcription factor. The POU5F1B retrogene on 8q24 and POU5F1 on 6p21 were significantly co-expressed. These results suggest that a pathway critical to self-renewal of embryonic stem cells may also have a role in the origin of cancer. Note: This abstract was not presented at the meeting. Citation Format: Joan Breyer, Daniel Dorset, Travis Clark, Kevin Bradley, Tiina Wahlfors, Kate McReynolds, William Maynard, Sam Chang, Michael Cookson, Joseph Smith, Johanna Schleutker, William Dupont, Jeffrey R. Smith. An expressed retrogene of master embryonic stem cell factor OCT4 alters prostate cancer susceptibility. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5067. doi:10.1158/1538-7445.AM2014-5067
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