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

被引：28

作者：

Breyer, Joan P. ^{[1
]}

Dorset, Daniel C. ^{[1
]}

Clark, Travis A. ^{[1
]}

Bradley, Kevin M. ^{[1
,2
]}

Wahlfors, Tiina A. ^{[3
,4
]}

McReynolds, Kate M. ^{[1
]}

Maynard, William H. ^{[1
]}

Chang, Sam S. ^{[5
]}

Cookson, Michael S. ^{[5
]}

Smith, Joseph A. ^{[5
]}

Schleutker, Johanna ^{[6
]}

Dupont, William D. ^{[7
]}

Smith, Jeffrey R. ^{[1
,8
]}

机构：

[1] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Dept Med, Nashville, TN 37232 USA

[2] Fdn Appl Mol Evolut, Gainesville, FL 32604 USA

[3] Univ Tampere, Inst Biomed Technol BioMediTech, Tampere 33520, Finland

[4] Fimlab Labs, Tampere 33520, Finland

[5] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Dept Urol Surg, Nashville, TN 37232 USA

[6] Univ Turku, Inst Biomed, Dept Med Biochem & Genet, Turku 20014, Finland

[7] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Dept Biostat, Nashville, TN 37232 USA

[8] Vet Affairs Tennessee Valley Healthcare Syst, Med Res Serv, Nashville, TN 37212 USA

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2014年 / 94卷 / 03期

基金：

芬兰科学院;

关键词：

GENOME-WIDE ASSOCIATION; LONG-RANGE INTERACTION; COLORECTAL-CANCER; SELF-RENEWAL; DIFFERENTIAL EXPRESSION; TUMOR-DEVELOPMENT; MYC EXPRESSION; 8Q24; PROSTATE; SNP RS6983267; MULTIPLE LOCI;

D O I：

10.1016/j.ajhg.2014.01.019

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：395 / 404

页数：10

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