دورية أكاديمية
Germline polymorphisms in an enhancer of PSIP1 are associated with progression-free survival in epithelial ovarian cancer
| العنوان: | Germline polymorphisms in an enhancer of PSIP1 are associated with progression-free survival in epithelial ovarian cancer |
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| المؤلفون: | French, JD, Johnatty, SE, Lu, Y, Beesley, J, Gao, B, Kalimutho, M, Henderson, MJ, Russell, AJ, Kar, S, Chen, X, Hillman, KM, Kaufmann, S, Sivakumaran, H, O'Reilly, M, Wang, C, Korbie, DJ, Lambrechts, D, Despierre, E, Van Nieuwenhuysen, E, Lambrechts, S, Vergote, I, Karlan, B, Lester, J, Orsulic, S, Walsh, C, Fasching, PA, Beckmann, MW, Ekici, AB, Hein, A, Matsuo, K, Hosono, S, Pisterer, J, Hillemanns, P, Nakanishi, T, Yatabe, Y, Goodman, MT, Lurie, G, Matsuno, RK, Thompson, PJ, Pejovic, T, Bean, Y, Heitz, F, Harter, P, Du Bois, A, Schwaab, I, Hogdall, E, Kjaer, SK, Jensen, A, Hogdall, C, Lundvall, L, Engelholm, SA, Brown, B, Flanagan, JM, Metcalf, MD, Siddiqui, N, Sellers, T, Fridley, B, Cunningham, J, Schildkraut, JM, Iversen, E, Weber, RP, Brennan, D, Berchuck, A, Pharoah, P, Harnett, P, Norris, MD, Haber, M, Goode, EL, Lee, JS, Khanna, KK, Meyer, KB, Chenevix-Trench, G, DeFazio, A, Edwards, SL, MacGregor, S |
| المصدر: | urn:ISSN:1949-2553 ; Oncotarget, 7, 6, 6353-6368 |
| بيانات النشر: | Impact Journals, LLC |
| سنة النشر: | 2016 |
| المجموعة: | UNSW Sydney (The University of New South Wales): UNSWorks |
| مصطلحات موضوعية: | Genetics, Ovarian Cancer, Rare Diseases, Human Genome, Cancer, 2 Aetiology, 2.1 Biological and endogenous factors, Adaptor Proteins, Signal Transducing, Apoptosis, Biomarkers, Tumor, Cell Proliferation, Chromatin Immunoprecipitation, Cohort Studies, Cystadenocarcinoma, Serous, Electrophoretic Mobility Shift Assay, Enhancer Elements, Genetic, Fallopian Tube Neoplasms, Female, Follow-Up Studies, Germ-Line Mutation, Humans, Ovarian Neoplasms, Peritoneal Neoplasms, Polymorphism, Single Nucleotide, Prognosis |
| الوصف: | Women with epithelial ovarian cancer (EOC) are usually treated with platinum/taxane therapy after cytoreductive surgery but there is considerable inter-individual variation in response. To identify germline single-nucleotide polymorphisms (SNPs) that contribute to variations in individual responses to chemotherapy, we carried out a multi-phase genome-wide association study (GWAS) in 1,244 women diagnosed with serous EOC who were treated with the same first-line chemotherapy, carboplatin and paclitaxel. We identified two SNPs (rs7874043 and rs72700653) in TTC39B (best P=7×10-5, HR=1.90, for rs7874043) associated with progression-free survival (PFS). Functional analyses show that both SNPs lie in a putative regulatory element (PRE) that physically interacts with the promoters of PSIP1, CCDC171 and an alternative promoter of TTC39B. The C allele of rs7874043 is associated with poor PFS and showed increased binding of the Sp1 transcription factor, which is critical for chromatin interactions with PSIP1. Silencing of PSIP1 significantly impaired DNA damage-induced Rad51 nuclear foci and reduced cell viability in ovarian cancer lines. PSIP1 (PC4 and SFRS1 Interacting Protein 1) is known to protect cells from stress-induced apoptosis, and high expression is associated with poor PFS in EOC patients. We therefore suggest that the minor allele of rs7874043 confers poor PFS by increasing PSIP1 expression. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | http://hdl.handle.net/1959.4/unsworks_79145Test; https://unsworks.unsw.edu.au/bitstreams/617e9e9d-1d41-4699-975f-67e351ebcc02/downloadTest; https://doi.org/10.18632/oncotarget.7047Test |
| DOI: | 10.18632/oncotarget.7047 |
| الإتاحة: | https://doi.org/10.18632/oncotarget.7047Test http://hdl.handle.net/1959.4/unsworks_79145Test https://unsworks.unsw.edu.au/bitstreams/617e9e9d-1d41-4699-975f-67e351ebcc02/downloadTest |
| حقوق: | open access ; https://purl.org/coar/access_right/c_abf2Test ; CC BY ; https://creativecommons.org/licenses/by/4.0Test/ ; free_to_read |
| رقم الانضمام: | edsbas.1C64A73A |
| قاعدة البيانات: | BASE |
| DOI: | 10.18632/oncotarget.7047 |
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