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Grant Details

Grant Number: 4R01CA157881-07 Interpret this number
Primary Investigator: Wang, Liang
Organization: Medical College Of Wisconsin
Project Title: Genetic Determinants of Gene Expression Phenotypes in Aggressive Prostate Cancer
Fiscal Year: 2016
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Abstract

DESCRIPTION (provided by applicant): The regulatory variation is believed to play an important role in shaping phenotypic differences among individuals and thus is also very likely to influence disease susceptibility and progression. In this study, we propose to take advantage of the expression QTL mapping and co-expressed gene network analysis to identify and characterize candidate genes and genetic variants that are responsible for aggressive phenotype of prostate cancer. Our hypothesis is that most genetic variants responsible for an aggressive phenotype of prostate cancer have regulatory effect on candidate gene expression and complete understanding of regulatory SNPs can only be achieved by examining primary tissue (here, prostate). To test this hypothesis, we will use a case-case study design and apply an innovative yet feasible approach by integrating DNA sequence variation and gene expression with clinical trait information. The four Specific Aims are: 1. Identify novel aggressiveness-related candidate SNPs by utilizing an expression genetics-based eQTL mapping approach; 2, Identify novel aggressiveness-related candidate SNPs by utilizing an integrative systems genetics-based network analysis approach; 3. For the novel candidate SNPs identified in Aims 1 and 2, perform additional association-based studies to confirm their association with an aggressiveness-related phenotype for prostate cancer; and 4. Identify candidate causal-SNPs by fine mapping, recognizing that the candidate eSNPs identified in Aim 3 will most likely be in linkage disequilibrium with the causal-SNPs. Understanding genetic mechanisms underlying the aggressive phenotype will have significant impact on prevention strategies, prognosis and potentially targeted therapy.

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Publications

Predisposes to Aggressive Prostate Cancer.
Authors: Sipeky C. , Gao P. , Zhang Q. , Wang L. , Ettala O. , Talala K.M. , Tammela T.L.J. , Auvinen A. , Wiklund F. , Wei G.H. , et al. .
Source: Clinical Cancer Research : An Official Journal Of The American Association For Cancer Research, 2018-09-04 00:00:00.0; , .
EPub date: 2018-09-04 00:00:00.0.
PMID: 30181389
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Biology and Clinical Implications of the 19q13 Aggressive Prostate Cancer Susceptibility Locus.
Authors: Gao P. , Xia J.H. , Sipeky C. , Dong X.M. , Zhang Q. , Yang Y. , Zhang P. , Cruz S.P. , Zhang K. , Zhu J. , et al. .
Source: Cell, 2018-07-26 00:00:00.0; 174(3), p. 576-589.e18.
EPub date: 2018-07-19 00:00:00.0.
PMID: 30033361
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High-throughput screening of prostate cancer risk loci by single nucleotide polymorphisms sequencing.
Authors: Zhang P. , Xia J.H. , Zhu J. , Gao P. , Tian Y.J. , Du M. , Guo Y.C. , Suleman S. , Zhang Q. , Kohli M. , et al. .
Source: Nature Communications, 2018-05-22 00:00:00.0; 9(1), p. 2022.
EPub date: 2018-05-22 00:00:00.0.
PMID: 29789573
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Network-directed cis-mediator analysis of normal prostate tissue expression profiles reveals downstream regulatory associations of prostate cancer susceptibility loci.
Authors: Larson N.B. , McDonnell S.K. , Fogarty Z. , Larson M.C. , Cheville J. , Riska S. , Baheti S. , Weber A.M. , Nair A.A. , Wang L. , et al. .
Source: Oncotarget, 2017-10-17 00:00:00.0; 8(49), p. 85896-85908.
EPub date: 2017-09-08 00:00:00.0.
PMID: 29156765
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Molecular characterization of cell-free eccDNAs in human plasma.
Authors: Zhu J. , Zhang F. , Du M. , Zhang P. , Fu S. , Wang L. .
Source: Scientific Reports, 2017-09-08 00:00:00.0; 7(1), p. 10968.
EPub date: 2017-09-08 00:00:00.0.
PMID: 28887493
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3c-digital Pcr For Quantification Of Chromatin Interactions
Authors: Du M. , Wang L. .
Source: Bmc Molecular Biology, 2016-12-06 00:00:00.0; 17(1), p. 23.
PMID: 27923366
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Mapping Complex Traits In A Diversity Outbred F1 Mouse Population Identifies Germline Modifiers Of Metastasis In Human Prostate Cancer
Authors: Winter J.M. , Gildea D.E. , Andreas J.P. , Gatti D.M. , Williams K.A. , Lee M. , Hu Y. , Zhang S. , NISC Comparative Sequencing Program , Mullikin J.C. , et al. .
Source: Cell Systems, 2016-11-25 00:00:00.0; , .
PMID: 27916600
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Mir-375 Induces Docetaxel Resistance In Prostate Cancer By Targeting Sec23a And Yap1
Authors: Wang Y. , Lieberman R. , Pan J. , Zhang Q. , Du M. , Zhang P. , Nevalainen M. , Kohli M. , Shenoy N.K. , Meng H. , et al. .
Source: Molecular Cancer, 2016-11-10 00:00:00.0; 15(1), p. 70.
PMID: 27832783
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Copy Number Variations In Urine Cell Free Dna As Biomarkers In Advanced Prostate Cancer
Authors: Xia Y. , Huang C.C. , Dittmar R. , Du M. , Wang Y. , Liu H. , Shenoy N. , Wang L. , Kohli M. .
Source: Oncotarget, 2016-06-14 00:00:00.0; 7(24), p. 35818-35831.
PMID: 27127882
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Chromatin interactions and candidate genes at ten prostate cancer risk loci.
Authors: Du M. , Tillmans L. , Gao J. , Gao P. , Yuan T. , Dittmar R.L. , Song W. , Yang Y. , Sahr N. , Wang T. , et al. .
Source: Scientific Reports, 2016-03-16 00:00:00.0; 6, p. 23202.
EPub date: 2016-03-16 00:00:00.0.
PMID: 26979803
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Plasma extracellular RNA profiles in healthy and cancer patients.
Authors: Yuan T. , Huang X. , Woodcock M. , Du M. , Dittmar R. , Wang Y. , Tsai S. , Kohli M. , Boardman L. , Patel T. , et al. .
Source: Scientific Reports, 2016-01-20 00:00:00.0; 6, p. 19413.
EPub date: 2016-01-20 00:00:00.0.
PMID: 26786760
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Identification of candidate genes for prostate cancer-risk SNPs utilizing a normal prostate tissue eQTL data set.
Authors: Thibodeau S.N. , French A.J. , McDonnell S.K. , Cheville J. , Middha S. , Tillmans L. , Riska S. , Baheti S. , Larson M.C. , Fogarty Z. , et al. .
Source: Nature Communications, 2015-11-27 00:00:00.0; 6, p. 8653.
EPub date: 2015-11-27 00:00:00.0.
PMID: 26611117
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A large multiethnic genome-wide association study of prostate cancer identifies novel risk variants and substantial ethnic differences.
Authors: Hoffmann T.J. , Van Den Eeden S.K. , Sakoda L.C. , Jorgenson E. , Habel L.A. , Graff R.E. , Passarelli M.N. , Cario C.L. , Emami N.C. , Chao C.R. , et al. .
Source: Cancer Discovery, 2015 Aug; 5(8), p. 878-91.
PMID: 26034056
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Plasma genetic and genomic abnormalities predict treatment response and clinical outcome in advanced prostate cancer.
Authors: Xia S. , Kohli M. , Du M. , Dittmar R.L. , Lee A. , Nandy D. , Yuan T. , Guo Y. , Wang Y. , Tschannen M.R. , et al. .
Source: Oncotarget, 2015-06-30 00:00:00.0; 6(18), p. 16411-21.
PMID: 25915538
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Comprehensively evaluating cis-regulatory variation in the human prostate transcriptome by using gene-level allele-specific expression.
Authors: Larson N.B. , McDonnell S. , French A.J. , Fogarty Z. , Cheville J. , Middha S. , Riska S. , Baheti S. , Nair A.A. , Wang L. , et al. .
Source: American Journal Of Human Genetics, 2015-06-04 00:00:00.0; 96(6), p. 869-82.
EPub date: 2015-06-04 00:00:00.0.
PMID: 25983244
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Exosomal miR-1290 and miR-375 as prognostic markers in castration-resistant prostate cancer.
Authors: Huang X. , Yuan T. , Liang M. , Du M. , Xia S. , Dittmar R. , Wang D. , See W. , Costello B.A. , Quevedo F. , et al. .
Source: European Urology, 2015 Jan; 67(1), p. 33-41.
PMID: 25129854
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Prostate cancer risk locus at 8q24 as a regulatory hub by physical interactions with multiple genomic loci across the genome.
Authors: Du M. , Yuan T. , Schilter K.F. , Dittmar R.L. , Mackinnon A. , Huang X. , Tschannen M. , Worthey E. , Jacob H. , Xia S. , et al. .
Source: Human Molecular Genetics, 2015-01-01 00:00:00.0; 24(1), p. 154-66.
EPub date: 2015-01-01 00:00:00.0.
PMID: 25149474
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eRNA: a graphic user interface-based tool optimized for large data analysis from high-throughput RNA sequencing.
Authors: Yuan T. , Huang X. , Dittmar R.L. , Du M. , Kohli M. , Boardman L. , Thibodeau S.N. , Wang L. .
Source: Bmc Genomics, 2014-03-05 00:00:00.0; 15, p. 176.
EPub date: 2014-03-05 00:00:00.0.
PMID: 24593312
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Extracellular microRNAs in urologic malignancies: chances and challenges.
Authors: Huang X. , Liang M. , Dittmar R. , Wang L. .
Source: International Journal Of Molecular Sciences, 2013-07-16 00:00:00.0; 14(7), p. 14785-99.
EPub date: 2013-07-16 00:00:00.0.
PMID: 23863690
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