An 8q24 gene desert variant associated with prostate cancer risk confers differential in vivo activity to a MYC enhancer.

Genome Research
Nora F WassermanMarcelo A Nobrega

Abstract

Genome-wide association studies (GWAS) routinely identify risk variants in noncoding DNA, as exemplified by reports of multiple single nucleotide polymorphisms (SNPs) associated with prostate cancer in five independent regions in a gene desert on 8q24. Two of these regions also have been associated with breast and colorectal cancer. These findings implicate functional variation within long-range cis-regulatory elements in disease etiology. We used an in vivo bacterial artificial chromosome (BAC) enhancer-trapping strategy in mice to scan a half-megabase of the 8q24 gene desert encompassing the prostate cancer-associated regions for long-range cis-regulatory elements. These BAC assays identified both prostate and mammary gland enhancer activities within the region. We demonstrate that the 8q24 cancer-associated variant rs6983267 lies within an in vivo prostate enhancer whose expression mimics that of the nearby MYC proto-oncogene. Additionally, we show that the cancer risk allele increases prostate enhancer activity in vivo relative to the non-risk allele. This allele-specific enhancer activity is detectable during early prostate development and throughout prostate maturation, raising the possibility that this SNP could assert i...Continue Reading

References

Jun 1, 1986·Biology of Reproduction·Y SugimuraA A Donjacour
Jan 1, 1993·Methods in Enzymology·D G Wilkinson, M A Nieto
Mar 22, 2003·Lancet·Angelo M DeMarzoJonathan I Epstein
Oct 18, 2003·Science·Marcelo A NobregaEdward M Rubin
Jan 1, 2004·Molecular and Cellular Biology·Magda A M Krajnc-FrankenJan A Gossen
May 12, 2005·Genomics·Francis PoulinLen A Pennacchio
Jun 7, 2005·The Prostate·Karin WilliamsSimon W Hayward
Aug 12, 2005·Nature Reviews. Genetics·James F Crow
Oct 19, 2005·Nature Reviews. Molecular Cell Biology·Lothar Hennighausen, Gertraud W Robinson
May 10, 2006·Nature Genetics·Laufey T AmundadottirKari Stefansson
Apr 3, 2007·Nature Genetics·Christopher A HaimanDavid Reich
May 29, 2007·Nature·Douglas F EastonBruce A J Ponder
Sep 19, 2007·Cancer Research·Jacques LapointeJonathan R Pollack
Jun 26, 2008·Journal of the National Cancer Institute·Maya GhoussainiUNKNOWN UK ProtecT Study Collaborators
Sep 17, 2008·Nature Genetics·Lambertus A KiemeneyKari Stefansson
Jan 30, 2009·JAMA : the Journal of the American Medical Association·Jun J YangMary V Relling
May 29, 2009·CA: a Cancer Journal for Clinicians·Ahmedin JemalMichael J Thun
Jun 25, 2009·Cancer Research·Mark M PomerantzMatthew L Freedman
Aug 15, 2009·PLoS Genetics·Li JiaGerhard A Coetzee
Sep 11, 2009·Nature·Axel ViselLen A Pennacchio
Sep 22, 2009·Nature Genetics·Ali Amin Al OlamaDouglas F Easton
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jose SoteloXiaolin Wu
Mar 31, 2010·Molecular Psychiatry·Y LiuUNKNOWN Wellcome Trust Case-Control Consortium

❮ Previous
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Citations

Mar 28, 2013·Pathology Oncology Research : POR·Ana S BrankovićStanka P Romac
Sep 8, 2010·Asian Journal of Andrology·Dolores J Lamb, Mounia Tannour-Louet
Mar 11, 2011·Journal of Human Genetics·Ioannis PolitopoulosAndrew Collins
Nov 10, 2012·Nature Biotechnology·Lucas D Ward, Manolis Kellis
Mar 29, 2013·Nature Genetics·Paul D P PharoahThomas A Sellers
May 27, 2011·Nature Genetics·Matthew L FreedmanIan G Mills
Mar 19, 2013·Nature Reviews. Genetics·Len A PennacchioGill Bejerano
Mar 2, 2011·The Pharmacogenomics Journal·C SunA Di Rienzo
Oct 30, 2013·Annals of Oncology : Official Journal of the European Society for Medical Oncology·P RizzoloL Ottini
Dec 6, 2011·Human Molecular Genetics·Xiaobo ZhouEdwin K Silverman
May 1, 2012·Human Molecular Genetics·Scott SmemoMarcelo A Nobrega
Oct 9, 2012·Nucleic Acids Research·Michael HillerGill Bejerano
Jun 15, 2013·Nucleic Acids Research·Nathan Harmston, Boris Lenhard
May 8, 2013·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Alvaro Rada-IglesiasJoanna Wysocka
Jun 16, 2011·Genome Research·Daniel SavicMarcelo A Nobrega
Jul 5, 2011·Journal of Gastroenterology and Hepatology·Monir Sadat HaerianBatoul Sadat Haerian
Dec 7, 2011·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Lucinda HughesVeda N Giri
Jun 19, 2012·The Journal of Clinical Investigation·Malou van den BoogaardVincent M Christoffels
Apr 4, 2013·BMC Genomics·Chao-Kung ChenFrançois Spitz
Jun 4, 2011·Genome Biology·Daniel ShrinerCharles N Rotimi
Jan 25, 2012·Genome Biology·Noboru Jo SakabeMarcelo A Nobrega
Oct 13, 2011·Genome Medicine·Rebecca Worsley-HuntWyeth W Wasserman
Apr 18, 2012·PloS One·Andrea BurriTim D Spector
Nov 13, 2012·PloS One·Miranda V McEwanJulia A Horsfield
Oct 11, 2011·The Cleft Palate-craniofacial Journal : Official Publication of the American Cleft Palate-Craniofacial Association·Masanori HikidaKoh-Ichiro Yoshiura
Sep 20, 2011·Personalized Medicine·Jian Gu, Xifeng Wu
Jul 31, 2013·International Journal of Molecular Sciences·James FarrellShiv Srivastava
Apr 13, 2011·World Journal of Gastroenterology : WJG·Yi GuoHeng-Jun Gao
Apr 26, 2014·World Journal of Gastroenterology : WJG·Kejin ZhangHushan Yang
Nov 23, 2013·Cardiovascular Research·Saagar Mahida
Mar 14, 2014·Current Atherosclerosis Reports·Clint L MillerThomas Quertermous

❮ Previous
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