An expressed retrogene of the master embryonic stem cell gene POU5F1 is associated with prostate cancer susceptibility.

Breyer JP, Dorset DC, Clark TA, Bradley KM, Wahlfors TA, McReynolds KM, Maynard WH, Chang SS, Cookson MS, Smith JA, Schleutker J, Dupont WD, Smith JR
Am J Hum Genet. 2014 94 (3): 395-404

PMID: 24581739 · PMCID: PMC3951923 · DOI:10.1016/j.ajhg.2014.01.019

Genetic association studies of prostate 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 POU5F1B 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 POU5F1B missense variants are also associated with risk of transformation. POU5F1 is known to be self-regulated by the encoded Oct4 transcription factor. We further observe that POU5F1 expression is directly correlated with POU5F1B 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.

Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

MeSH Terms (26)

Adolescent Adult Aged Alleles Case-Control Studies Cell Nucleus Cell Transformation, Neoplastic Databases, Genetic Embryonic Stem Cells Gene Expression Regulation, Neoplastic Genetic Predisposition to Disease Genetic Variation Genotype Haplotypes Humans Male Middle Aged Mutation, Missense Octamer Transcription Factor-3 Open Reading Frames Prostatic Neoplasms Quantitative Trait Loci Risk Sequence Analysis, DNA Transcription, Genetic Young Adult

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