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Grant Details

Grant Number: 1R01CA250018-01 Interpret this number
Primary Investigator: Wang, Liang
Organization: H. Lee Moffitt Cancer Ctr & Res Inst
Project Title: Functional Characterization of Prostate Cancer Risk Loci By High Throughput Sequencing
Fiscal Year: 2020


Abstract

SUMMARY Although the causes of human cancers are attributable to many factors, there is substantial evidence that genetics likely plays a key role. Previous studies have used population-based approaches, such as genome- wide association studies (GWASs), to identify cancer-associated genetic susceptibility variants (single nucleotide polymorphisms or SNPs) in the human genome. Although GWASs have reported thousands of SNP loci associated with an increased cancer risk, functional effects of these risk-SNPs remain largely unknown. Because many of the risk-SNPs are located in genomic regions without known protein-coding genes and some reside several hundred kilobases from any nearby gene, it is believed that many, if not most, of these SNPs have regulatory effects on the genes that cause these cancers. To identify regulatory SNPs responsible for the disease risk, we propose to apply two novel high-throughput sequencing technologies to screen thousands of candidate SNPs at prostate cancer risk loci. Aim 1 is to determine SNP-dependent transcription factor (TF) binding differences at prostate cancer risk loci through IP-SNPs-seq. Aim 2 is to determine biological significance of SNP-dependent sequence variants at prostate cancer risk loci through CRISPRi-SNPs-seq. Aim 3 is to functionally characterize a set of selected SNPs and their target genes. Successful completion of the proposed study will gain further understanding of the functional role of GWAS-implicated SNPs. Characterization of the functional effects of cancer risk loci will facilitate the translation of population-based discovery into biological mechanisms and will eventually benefit clinical practice.



Publications

5-hydroxymethylcytosine sequencing in plasma cell-free DNA identifies unique epigenomic features in prostate cancer patients resistant to androgen deprivation therapy.
Authors: Li Q. , Huang C.C. , Huang S. , Tian Y. , Huang J. , Bitaraf A. , Dong X. , Nevalanen M.T. , Zhang J. , Manley B.J. , et al. .
Source: medRxiv : the preprint server for health sciences, 2023-10-16; , .
EPub date: 2023-10-16.
PMID: 37904926
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Combined CRISPRi and proteomics screening reveal a cohesin-CTCF-bound allele contributing to increased expression of RUVBL1 and prostate cancer progression.
Authors: Tian Y. , Dong D. , Wang Z. , Wu L. , Park J.Y. , PRACTICAL consortium , Wei G.H. , Wang L. .
Source: American journal of human genetics, 2023-08-03; 110(8), p. 1289-1303.
PMID: 37541187
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Extensive germline-somatic interplay contributes to prostate cancer progression through HNF1B co-option of TMPRSS2-ERG.
Authors: Giannareas N. , Zhang Q. , Yang X. , Na R. , Tian Y. , Yang Y. , Ruan X. , Huang D. , Yang X. , Wang C. , et al. .
Source: Nature communications, 2022-11-28; 13(1), p. 7320.
EPub date: 2022-11-28.
PMID: 36443337
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Novel role of prostate cancer risk variant rs7247241 on PPP1R14A isoform transition through allelic TF binding and CpG methylation.
Authors: Tian Y. , Soupir A. , Liu Q. , Wu L. , Huang C.C. , Park J.Y. , Wang L. .
Source: Human molecular genetics, 2022-05-19; 31(10), p. 1610-1621.
PMID: 34849858
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Clinical Applications of Liquid Biopsy in Prostate Cancer: From Screening to Predictive Biomarker.
Authors: Ionescu F. , Zhang J. , Wang L. .
Source: Cancers, 2022-03-29; 14(7), .
EPub date: 2022-03-29.
PMID: 35406500
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Cancer Detection and Classification by CpG Island Hypermethylation Signatures in Plasma Cell-Free DNA.
Authors: Huang J. , Soupir A.C. , Schlick B.D. , Teng M. , Sahin I.H. , Permuth J.B. , Siegel E.M. , Manley B.J. , Pellini B. , Wang L. .
Source: Cancers, 2021-11-09; 13(22), .
EPub date: 2021-11-09.
PMID: 34830765
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