|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|
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.
Comprehensively evaluating cis-regulatory variation in the human prostate transcriptome by using gene-level allele-specific expression.
Authors: Larson NB, McDonnell S, French AJ, Fogarty Z, Cheville J, Middha S, Riska S, Baheti S, Nair AA, Wang L, Schaid DJ, Thibodeau SN
Source: Am J Hum Genet, 2015 Jun 4;96(6), p. 869-82.
EPub date: 2015 May 14.
Plasma genetic and genomic abnormalities predict treatment response and clinical outcome in advanced prostate cancer.
Authors: Xia S, Kohli M, Du M, Dittmar RL, Lee A, Nandy D, Yuan T, Guo Y, Wang Y, Tschannen MR, Worthey E, Jacob H, See W, Kilari D, Wang X, Hovey RL, Huang CC, Wang L
Source: Oncotarget, 2015 Jun 30;6(18), p. 16411-21.
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 KF, Dittmar RL, Mackinnon A, Huang X, Tschannen M, Worthey E, Jacob H, Xia S, Gao J, Tillmans L, Lu Y, Liu P, Thibodeau SN, Wang L
Source: Hum Mol Genet, 2015 Jan 1;24(1), p. 154-66.
EPub date: 2014 Aug 22.
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 BA, Quevedo F, Tan W, Nandy D, Bevan GH, Longenbach S, Sun Z, Lu Y, Wang T, Thibodeau SN, Boardman L, Kohli M, Wang L
Source: Eur Urol, 2015 Jan;67(1), p. 33-41.
EPub date: 2014 Aug 14.
eRNA: a graphic user interface-based tool optimized for large data analysis from high-throughput RNA sequencing.
Authors: Yuan T, Huang X, Dittmar RL, Du M, Kohli M, Boardman L, Thibodeau SN, Wang L
Source: BMC Genomics, 2014 Mar 5;15, p. 176.
EPub date: 2014 Mar 5.
Extracellular microRNAs in urologic malignancies: chances and challenges.
Authors: Huang X, Liang M, Dittmar R, Wang L
Source: Int J Mol Sci, 2013 Jul 16;14(7), p. 14785-99.
EPub date: 2013 Jul 16.