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National Institutes of Health: National Cancer Institute: Division of Cancer Control and Population Sciences
Grant Details

Grant Number: 5R01CA157881-04 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: 2013
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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

Extracellular Micrornas In Urologic Malignancies: Chances And Challenges
Authors: Huang X. , Liang M. , Dittmar R. , Wang L. .
Source: International Journal Of Molecular Sciences, 2013; 14(7), p. 14785-99.
PMID: 23863690
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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; 15, p. 176.
PMID: 24593312
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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.
PMID: 25149474
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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.
PMID: 25983244
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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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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; 6, p. 8653.
PMID: 26611117
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