Publications
177 results found
Glasspool RM, Brown R, Gore ME, et al., 2014, A randomised, phase II trial of the DNA-hypomethylating agent 5-aza-2 '-deoxycytidine (decitabine) in combination with carboplatin vs carboplatin alone in patients with recurrent, partially platinum-sensitive ovarian cancer, British Journal of Cancer, Vol: 110, Pages: 1923-1929, ISSN: 1532-1827
Background: Our previous laboratory and clinical data suggested that one mechanism underlying the development of platinum resistance inovarian cancer is the acquisition of DNA methylation. We therefore tested the hypothesis that the DNA hypomethylating agent 5-aza-20-deoxycytodine (decitabine) can reverse resistance to carboplatin in women with relapsed ovarian cancer.Methods: Patients progressing 6–12 months after previous platinum therapy were randomised to decitabine on day 1 and carboplatin (AUC 6) onday 8, every 28 days or carboplatin alone. The primary objective was response rate in patients with methylated hMLH1 tumour DNA in plasma.Results: After a pre-defined interim analysis, the study closed due to lack of efficacy and poor treatment deliverability in 15 patients treated withthe combination. Responses by GCIG criteria were 9 out of 14 vs 3 out of 15 and by RECIST were 6 out of 13 vs 1 out of 12 for carboplatin andcarboplatin/decitabine, respectively. Grade 3/4 neutropenia was more common with the combination (60% vs 15.4%) as was G2/3 carboplatinhypersensitivity (47% vs 21%).Conclusions: With this schedule, the addition of decitabine appears to reduce rather than increase the efficacy of carboplatin in partiallyplatinum-sensitive ovarian cancer and is difficult to deliver. Patient-selection strategies, different schedules and other demethylating agents shouldbe considered in future combination studies.
Charbonneau B, Block MS, Bamlet WR, et al., 2014, Risk of Ovarian Cancer and the NF-κB Pathway: Genetic Association with <i>IL1A</i> and <i>TNFSF10</i>, CANCER RESEARCH, Vol: 74, Pages: 852-861, ISSN: 0008-5472
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- Citations: 36
Sriraksa R, Zeller C, Dai W, et al., 2013, Aberrant DNA Methylation at Genes Associated with a Stem Cell-like Phenotype in Cholangiocarcinoma Tumors, CANCER PREVENTION RESEARCH, Vol: 6, Pages: 1348-1355, ISSN: 1940-6207
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- Citations: 24
Cherblanc FL, Chapman KL, Reid J, et al., 2013, On the Histone Lysine Methyltransferase Activity of Fungal Metabolite Chaetocin, JOURNAL OF MEDICINAL CHEMISTRY, Vol: 56, Pages: 8616-8625, ISSN: 0022-2623
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- Citations: 48
McWhinney-Glass S, Winham SJ, Hertz DL, et al., 2013, Cumulative Genetic Risk Predicts Platinum/Taxane-Induced Neurotoxicity, CLINICAL CANCER RESEARCH, Vol: 19, Pages: 5769-5776, ISSN: 1078-0432
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- Citations: 26
Dai W, Zeller C, Masrour N, et al., 2013, Promoter CpG Island Methylation of Genes in Key Cancer Pathways Associates with Clinical Outcome in High-Grade Serous Ovarian Cancer, CLINICAL CANCER RESEARCH, Vol: 19, Pages: 5788-5797, ISSN: 1078-0432
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- Citations: 40
Flanagan JM, Wilhelm-Benartzi CS, Metcalf M, et al., 2013, Association of somatic DNA methylation variability with progression-free survival and toxicity in ovarian cancer patients., Annals of Oncology, Vol: 24, Pages: 2813-2818, ISSN: 1569-8041
Johnatty S, Beesley J, Gao B, et al., 2013, ABCB1 (MDR1) polymorphisms and ovarian cancer progression and survival: A comprehensive analysis from the Ovarian Cancer Association Consortium and The Cancer Genome Atlas, GYNECOLOGIC ONCOLOGY, Vol: 131, Pages: 8-14, ISSN: 0090-8258
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- Citations: 48
Hall JA, Brown R, 2013, Developing translational research infrastructure and capabilities associated with cancer clinical trials, EXPERT REVIEWS IN MOLECULAR MEDICINE, Vol: 15, ISSN: 1462-3994
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- Citations: 4
Shenker NS, Ueland PM, Polidoro S, et al., 2013, DNA Methylation as a Long-term Biomarker of Exposure to Tobacco Smoke, EPIDEMIOLOGY, Vol: 24, Pages: 712-716, ISSN: 1044-3983
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- Citations: 130
Wilhelm-Benartzi CS, Koestler DC, Karagas MR, et al., 2013, Review of processing and analysis methods for DNA methylation array data, British Journal of Cancer, Vol: 109, Pages: 1394-1402, ISSN: 1532-1827
The promise of epigenome-wide association studies and cancer-specific somatic DNA methylation changes in improving our understanding of cancer, coupled with the decreasing cost and increasing coverage of DNA methylation microarrays, has brought about a surge in the use of these technologies. Here, we aim to provide both a review of issues encountered in the processing and analysis of array-based DNA methylation data and a summary of the advantages of recent approaches proposed for handling those issues, focusing on approaches publicly available in open-source environments such as R and Bioconductor. We hope that the processing tools and analysis flowchart described herein will facilitate researchers to effectively use these powerful DNA methylation array-based platforms, thereby advancing our understanding of human health and disease.
Borley J, Ghaem-Maghami S, Brown R, 2013, Hypomethylation of MSX1 is associated with decreased gene expression, poor progression free survival and chemotherapy resistance in serous ovarian cancer, BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 120, Pages: 249-249, ISSN: 1470-0328
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- Citations: 1
White KL, Vierkant RA, Fogarty ZC, et al., 2013, Analysis of Over 10,000 Cases Finds No Association between Previously Reported Candidate Polymorphisms and Ovarian Cancer Outcome, CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, Vol: 22, Pages: 987-992, ISSN: 1055-9965
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- Citations: 18
Bojesen SE, Pooley KA, Johnatty SE, et al., 2013, Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer, NATURE GENETICS, Vol: 45, Pages: 371-384, ISSN: 1061-4036
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- Citations: 426
Stemke-Hale K, Shipman K, Kitsou-Mylona I, et al., 2013, Frequency of mutations and polymorphisms in borderline ovarian tumors of known cancer genes, MODERN PATHOLOGY, Vol: 26, Pages: 544-552, ISSN: 0893-3952
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- Citations: 14
Permuth-Wey J, Lawrenson K, Shen HC, et al., 2013, Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31, Nature Communications, Vol: 4, ISSN: 2041-1723
Epithelial ovarian cancer (EOC) has a heritable component that remains to be fully characterized. Most identified common susceptibility variants lie in non-protein-coding sequences. We hypothesized that variants in the 3′ untranslated region at putative microRNA (miRNA)-binding sites represent functional targets that influence EOC susceptibility. Here, we evaluate the association between 767 miRNA-related single-nucleotide polymorphisms (miRSNPs) and EOC risk in 18,174 EOC cases and 26,134 controls from 43 studies genotyped through the Collaborative Oncological Gene–environment Study. We identify several miRSNPs associated with invasive serous EOC risk (odds ratio=1.12, P=10−8) mapping to an inversion polymorphism at 17q21.31. Additional genotyping of non-miRSNPs at 17q21.31 reveals stronger signals outside the inversion (P=10−10). Variation at 17q21.31 is associated with neurological diseases, and our collaboration is the first to report an association with EOC susceptibility. An integrated molecular analysis in this region provides evidence for ARHGAP27 and PLEKHM1 as candidate EOC susceptibility genes.
Pharoah PDP, Tsai Y-Y, Ramus SJ, et al., 2013, GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer, Nature Genetics, Vol: 45, Pages: 362-370, ISSN: 1546-1718
Genome-wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC), with another two suggestive loci reaching near genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the UK. We selected the top 24,551 SNPs for inclusion on the iCOGS custom genotyping array. We performed follow-up genotyping in 18,174 individuals with EOC (cases) and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. We validated the two loci at 3q25 and 17q21 that were previously found to have associations close to genome-wide significance and identified three loci newly associated with risk: two loci associated with all EOC subtypes at 8q21 (rs11782652, P = 5.5 × 10−9) and 10p12 (rs1243180, P = 1.8 × 10−8) and another locus specific to the serous subtype at 17q12 (rs757210, P = 8.1 × 10−10). An integrated molecular analysis of genes and regulatory regions at these loci provided evidence for functional mechanisms underlying susceptibility and implicated CHMP4C in the pathogenesis of ovarian cancer.
Shenker NS, Polidoro S, van Veldhoven K, et al., 2013, Epigenome-wide association study in the European Prospective Investigation into Cancer and Nutrition (EPIC-Turin) identifies novel genetic loci associated with smoking, HUMAN MOLECULAR GENETICS, Vol: 22, Pages: 843-851, ISSN: 0964-6906
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- Citations: 304
Shen H, Fridley BL, Song H, et al., 2013, Epigenetic analysis leads to identification of <i>HNF1B</i> as a subtype-specific susceptibility gene for ovarian cancer, NATURE COMMUNICATIONS, Vol: 4, ISSN: 2041-1723
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- Citations: 131
Zeller C, Dai W, Curry E, et al., 2013, The DNA Methylomes of Serous Borderline Tumors Reveal Subgroups With Malignant- or Benign-Like Profiles, AMERICAN JOURNAL OF PATHOLOGY, Vol: 182, Pages: 668-677, ISSN: 0002-9440
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- Citations: 11
Cherblanc F, Chapman KL, Brown R, et al., 2013, Chaetocin is a nonspecific inhibitor of histone lysine methyltransferases, Nature Chemical Biology, Vol: 9, Pages: 136-137
Brown R, Kerr K, Haoudi A, et al., 2012, Tackling cancer burden in the Middle East: Qatar as an example, LANCET ONCOLOGY, Vol: 13, Pages: E501-E508, ISSN: 1470-2045
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- Citations: 38
Zeller C, Dai W, Steele NL, et al., 2012, Candidate DNA methylation drivers of acquired cisplatin resistance in ovarian cancer identified by methylome and expression profiling, ONCOGENE, Vol: 31, Pages: 4567-4576, ISSN: 0950-9232
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- Citations: 197
Borley J, Wilhelm-Benartzi C, Brown R, et al., 2012, Does tumour biology determine surgical success in the treatment of epithelial ovarian cancer? A systematic literature review, BRITISH JOURNAL OF CANCER, Vol: 107, Pages: 1069-1074, ISSN: 0007-0920
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- Citations: 44
Chapman-Rothe N, Curry E, Zeller C, et al., 2012, Chromatin H3K27me3/H3K4me3 histone marks define gene sets in high grade serous ovarian cancer that distinguish malignant, tumour sustaining and chemo-resistant ovarian tumour cells, Oncogene
Polidoro S, Shenker N, van Veldhoven K, et al., 2012, Epigenome-wide Association Study in the European Prospective Investigation Into Cancer and Nutrition (EPIC-Turin) Identifies Novel Genes Associated With Smoking, 22nd Biennial Congress of the European-Association-for-Cancer-Research, Publisher: ELSEVIER SCI LTD, Pages: S124-S125, ISSN: 0959-8049
Brennan K, Garcia-Closas M, Orr N, et al., 2012, Intragenic ATM Methylation in Peripheral Blood DNA as a Biomarker of Breast Cancer Risk, CANCER RESEARCH, Vol: 72, Pages: 2304-2313, ISSN: 0008-5472
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- Citations: 115
Brennan K, Garcias-Closas M, Orr N, et al., 2012, Intragenic ATM methylation in peripheral blood DNA as a biomarker of breast cancer risk, CANCER RESEARCH, Vol: 72, ISSN: 0008-5472
Cosentino L, Masrour N, Burns J, et al., 2012, Cotreatment with decitabine and paclitaxel is affected by the re-expression of drug-metabolising enzymes, CANCER RESEARCH, Vol: 72, ISSN: 0008-5472
Cherblanc F, Chapman-Rothe N, Brown R, et al., 2012, Current limitations and future opportunities for epigenetic therapies, Future Medicinal Chemistry, Vol: 4, Pages: 425-446
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