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dc.contributor.authorLai, John
dc.contributor.authorMoya, Leire
dc.contributor.authorAn, Jiyuan
dc.contributor.authorHoffman, Andrea
dc.contributor.authorSrinivasan, Srilakshmi
dc.contributor.authorPanchadsaram, Janaththani
dc.contributor.authorWalpole, Carina
dc.contributor.authorPerry-Keene, Joanna L
dc.contributor.authorChambers, Suzanne
dc.contributor.authorLehman, Melanie L
dc.contributor.authorNelson, Colleen C
dc.contributor.authorClements, Judith A
dc.contributor.authorBatra, Jyotsna
dc.date.accessioned2018-03-26T03:49:44Z
dc.date.available2018-03-26T03:49:44Z
dc.date.issued2017
dc.identifier.issn2045-2322
dc.identifier.doi10.1038/s41598-017-16700-y
dc.identifier.urihttp://hdl.handle.net/10072/372356
dc.description.abstractShort tandem repeats (STRs) are repetitive sequences of a polymorphic stretch of two to six nucleotides. We hypothesized that STRs are associated with prostate cancer development and/or progression. We undertook RNA sequencing analysis of prostate tumors and adjacent non-malignant cells to identify polymorphic STRs that are readily expressed in these cells. Most of the expressed STRs in the clinical samples mapped to intronic and intergenic DNA. Our analysis indicated that three of these STRs (TAAA-ACTG2, TTTTG-TRIB1, and TG-PCA3) are polymorphic and differentially expressed in prostate tumors compared to adjacent non-malignant cells. TG-PCA3 STR expression was repressed by the anti-androgen drug enzalutamide in prostate cancer cells. Genetic analysis of prostate cancer patients and healthy controls (N > 2,000) showed a significant association of the most common 11 repeat allele of TG-PCA3 STR with prostate cancer risk (OR = 1.49; 95% CI 1.11–1.99; P = 0.008). A significant association was also observed with aggressive disease (OR = 2.00; 95% CI 1.06–3.76; P = 0.031) and high mortality rates (HR = 3.0; 95% CI 1.03–8.77; P = 0.045). We propose that TG-PCA3 STR has both diagnostic and prognostic potential for prostate cancer. We provided a proof of concept to be applied to other RNA sequencing datasets to identify disease-associated STRs for future clinical exploratory studies.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherNature Publishing Group
dc.relation.ispartofpagefrom16862-1
dc.relation.ispartofpageto16862-14
dc.relation.ispartofjournalScientific Reports
dc.relation.ispartofvolume7
dc.subject.fieldofresearchBiochemistry and Cell Biology not elsewhere classified
dc.subject.fieldofresearchcode060199
dc.titleA microsatellite repeat in PCA3 long non-coding RNA is associated with prostate cancer risk and aggressiveness
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© Te Author(s) 2017. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
gro.hasfulltextFull Text
gro.griffith.authorChambers, Suzanne K.
gro.griffith.authorAn, Jay


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