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prostate cancer CNV

Prevathe Poniah, Shamsul Mohd Zain, Azad Hassan Abdul Razack, Shanggar Kuppusamy, Shankar Karuppayah, Hooi Sian Eng, Zahurin Mohamed
BACKGROUND: Two key issues in prostate cancer (PCa) that demand attention currently are the need for a more precise and minimally invasive screening test owing to the inaccuracy of prostate-specific antigen and differential diagnosis to distinguish advanced vs. indolent cancers. This continues to pose a tremendous challenge in diagnosis and prognosis of PCa and could potentially lead to overdiagnosis and overtreatment complications. Copy number variations (CNVs) in the human genome have been linked to various carcinomas including PCa...
May 17, 2017: Urologic Oncology
Armin Soave, Felix K-H Chun, Timo Hillebrand, Michael Rink, Lars Weisbach, Bettina Steinbach, Margit Fisch, Klaus Pantel, Heidi Schwarzenbach
The aim of the present study was to establish a rapid profiling method using multiplex ligation-dependent probe amplification (MLPA) and characterize copy number variations (CNV) in circulating, cell-free DNA (cfDNA) in 85 urothelial carcinoma of the bladder (UCB) patients treated with radical cystectomy (RC). MLPA was tested for the use of cfDNA extracted from serum and plasma by various commercial extraction kits. Eighteen probes served as reference to control denaturation, ligation and amplification efficiency...
May 7, 2017: Oncotarget
Stephanie B Greene, Angel E Dago, Laura J Leitz, Yipeng Wang, Jerry Lee, Shannon L Werner, Steven Gendreau, Premal Patel, Shidong Jia, Liangxuan Zhang, Eric K Tucker, Michael Malchiodi, Ryon P Graf, Ryan Dittamore, Dena Marrinucci, Mark Landers
Genomic instability is a hallmark of cancer often associated with poor patient outcome and resistance to targeted therapy. Assessment of genomic instability in bulk tumor or biopsy can be complicated due to sample availability, surrounding tissue contamination, or tumor heterogeneity. The Epic Sciences circulating tumor cell (CTC) platform utilizes a non-enrichment based approach for the detection and characterization of rare tumor cells in clinical blood samples. Genomic profiling of individual CTCs could provide a portrait of cancer heterogeneity, identify clonal and sub-clonal drivers, and monitor disease progression...
2016: PloS One
Mark D Long, Moray J Campbell
Nuclear receptors (NR) act as an integrated conduit for environmental and hormonal signals to govern genomic responses, which relate to cell fate decisions. We review how their integrated actions with each other, shared co-factors and other transcription factors are disrupted in cancer. Steroid hormone nuclear receptors are oncogenic drivers in breast and prostate cancer and blockade of signaling is a major therapeutic goal. By contrast to blockade of receptors, in other cancers enhanced receptor function is attractive, as illustrated initially with targeting of retinoic acid receptors in leukemia...
December 2015: Nuclear Receptor Research
Virpi H Laitinen, Oyediran Akinrinade, Tommi Rantapero, Teuvo L J Tammela, Tiina Wahlfors, Johanna Schleutker
BACKGROUND: The inherited factors that predispose individuals to prostate cancer (PrCa) remain largely unknown. The aim of this study was to identify germline copy number variants (CNVs) in Finnish individuals that could contribute to an increased PrCa risk. METHODS: Genome-wide CNV screening was performed by analyzing single nucleotide polymorphisms from 105 PrCa patients and 37 unaffected relatives, representing 31 Finnish hereditary PrCa (HPC) families. The CNVs that aggregated in affected individuals and overlapped with genes implicated in cancer were validated using quantitative PCR in 189 index patients from Finnish HPC families and in 476 controls...
February 15, 2016: Prostate
Yan P Yu, Silvia Liu, Zhiguang Huo, Amantha Martin, Joel B Nelson, George C Tseng, Jian-Hua Luo
Accurate prediction of prostate cancer clinical courses remains elusive. In this study, we performed whole genome copy number analysis on leukocytes of 273 prostate cancer patients using Affymetrix SNP6.0 chip. Copy number variations (CNV) were found across all chromosomes of the human genome. An average of 152 CNV fragments per genome was identified in the leukocytes from prostate cancer patients. The size distributions of CNV in the genome of leukocytes were highly correlative with prostate cancer aggressiveness...
2015: PloS One
S Salvi, V Casadio, V Conteduca, S L Burgio, C Menna, E Bianchi, L Rossi, E Carretta, C Masini, D Amadori, D Calistri, G Attard, U De Giorgi
BACKGROUND: This study aimed to investigate copy number variations (CNVs) of CYP17A1 and androgen receptor (AR) genes in serum cell-free DNA collected before starting abiraterone in 53 consecutive patients with castration-resistant prostate cancer (CRPC). METHODS: Serum DNA was isolated and CNVs were analysed for AR and CYP17A1 genes using Taqman copy number assays. The association between CNVs and progression-free/overall survival (PFS/OS) was evaluated by the Kaplan-Meier method and log-rank test...
May 12, 2015: British Journal of Cancer
James Coates, Asha K Jeyaseelan, Norma Ybarra, Marc David, Sergio Faria, Luis Souhami, Fabio Cury, Marie Duclos, Issam El Naqa
BACKGROUND AND PURPOSE: We explore analytical and data-driven approaches to investigate the integration of genetic variations (single nucleotide polymorphisms [SNPs] and copy number variations [CNVs]) with dosimetric and clinical variables in modeling radiation-induced rectal bleeding (RB) and erectile dysfunction (ED) in prostate cancer patients. MATERIALS AND METHODS: Sixty-two patients who underwent curative hypofractionated radiotherapy (66 Gy in 22 fractions) between 2002 and 2010 were retrospectively genotyped for CNV and SNP rs5489 in the xrcc1 DNA repair gene...
April 2015: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
Chinyere Ibeawuchi, Hartmut Schmidt, Reinhard Voss, Ulf Titze, Mahmoud Abbas, Joerg Neumann, Elke Eltze, Agnes Marije Hoogland, Guido Jenster, Burkhard Brandt, Axel Semjonow
The multifocal nature of prostate cancer (PCa) creates a challenge to patients' outcome prediction and their clinical management. An approach that scrutinizes every cancer focus is needed in order to generate a comprehensive evaluation of the disease, and by correlating to patients' clinico-pathological information, specific prognostic biomarker can be identified. Our study utilized the Affymetrix SNP 6.0 Genome-wide assay to investigate forty-three fresh frozen PCa tissue foci from twenty-three patients. With a long clinical follow-up period that ranged from 2...
February 11, 2015: International Journal of Molecular Sciences
Elise Emeville, Cédric Broquère, Laurent Brureau, Séverine Ferdinand, Pascal Blanchet, Luc Multigner, Marc Romana
BACKGROUND: Deletions of the glutathione S-transferase genes M1 and T1 (GSTM1 and GSTT1) have been studied as potential risk factors for prostate cancer. Conflicting results have been obtained. Moreover, most such studies could not discriminate heterozygous from homozygous carriers of the non-deleted alleles. OBJECTIVE: We investigated whether copy number variation (CNV) of the GSTM1 and/or GSTT1 genes contribute to the risk of prostate cancer in the Caribbean population of African descent of Guadeloupe...
2014: PloS One
Angel E Dago, Asya Stepansky, Anders Carlsson, Madelyn Luttgen, Jude Kendall, Timour Baslan, Anand Kolatkar, Michael Wigler, Kelly Bethel, Mitchell E Gross, James Hicks, Peter Kuhn
Timely characterization of a cancer's evolution is required to predict treatment efficacy and to detect resistance early. High content analysis of single Circulating Tumor Cells (CTCs) enables sequential characterization of genotypic, morphometric and protein expression alterations in real time over the course of cancer treatment. This concept was investigated in a patient with castrate-resistant prostate cancer progressing through both chemotherapy and targeted therapy. In this case study, we integrate across four timepoints 41 genome-wide copy number variation (CNV) profiles plus morphometric parameters and androgen receptor (AR) protein levels...
2014: PloS One
Delores J Grant, Cathrine Hoyo, Shannon D Oliver, Leah Gerber, Katie Shuler, Elizabeth Calloway, Alexis R Gaines, Megan McPhail, Jonathan N Livingston, Ricardo M Richardson, Joellen M Schildkraut, Stephen J Freedland
AIMS: Uridine diphosphate-glucuronosyltransferase 2B (UGT2B) enzymes conjugate testosterone metabolites to enable their excretion in humans. The functional significance of the UGT2B genetic variants has never been described in humans. We evaluated UGT2B variants in relation to plasma androstane-3α,17β-diol-glucuronide (AAG) levels and the prostate cancer risk. RESULTS: AAG levels were measured in sera from 150 controls and compared to the polymorphisms of UGT2B17, UGT2B15, and UGT2B7...
January 2013: Genetic Testing and Molecular Biomarkers
Elisa M Ledet, Xiaofeng Hu, Oliver Sartor, Walter Rayford, Marilyn Li, Diptasri Mandal
BACKGROUND: Prostate cancer is a complex multi-allelic disease and the most common malignancy in men. The incidence of prostate cancer in African American men is more than twice as high as that of any other race. Despite the high prevalence of prostate cancer amongst African American men, this population has been under represented in genetic studies of prostate cancer. Although genomic copy number variations (CNVs) have been detected in prostate tumors, this is the first study describing germline CNVs in African American hereditary prostate cancer families...
May 2013: Prostate
Yan P Yu, Chi Song, George Tseng, Bao Guo Ren, William LaFramboise, George Michalopoulos, Joel Nelson, Jian-Hua Luo
The prediction of prostate cancer clinical outcome remains a major challenge after the diagnosis, even with improved early detection by prostate-specific antigen (PSA) monitoring. To evaluate whether copy number variation (CNV) of the genomes in prostate cancer tumor, in benign prostate tissues adjacent to the tumor (AT), and in the blood of patients with prostate cancer predicts biochemical (PSA) relapse and the kinetics of relapse, 241 samples (104 tumor, 49 matched AT, 85 matched blood, and 3 cell lines) were analyzed using Affymetrix SNP 6...
June 2012: American Journal of Pathology
Ana Cv Krepischi, Maria Isabel W Achatz, Erika Mm Santos, Silvia S Costa, Bianca Cg Lisboa, Helena Brentani, Tiago M Santos, Amanda Gonçalves, Amanda F Nóbrega, Peter L Pearson, Angela M Vianna-Morgante, Dirce M Carraro, Ricardo R Brentani, Carla Rosenberg
INTRODUCTION: Genetic factors predisposing individuals to cancer remain elusive in the majority of patients with a familial or clinical history suggestive of hereditary breast cancer. Germline DNA copy number variation (CNV) has recently been implicated in predisposition to cancers such as neuroblastomas as well as prostate and colorectal cancer. We evaluated the role of germline CNVs in breast cancer susceptibility, in particular those with low population frequencies (rare CNVs), which are more likely to cause disease...
2012: Breast Cancer Research: BCR
Ka-Po Tse, Wen-Hui Su, Min-lee Yang, Hsiao-Yun Cheng, Ngan-Ming Tsang, Kai-Ping Chang, Sheng-Po Hao, Yin Yao Shugart, Yu-Sun Chang
Copy number variations (CNVs), a major source of human genetic polymorphism, have been suggested to have an important role in genetic susceptibility to common diseases such as cancer, immune diseases and neurological disorders. Nasopharyngeal carcinoma (NPC) is a multifactorial tumor closely associated with genetic background and with a male preponderance over female (3:1). Previous genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) that are associated with NPC susceptibility...
July 15, 2011: Human Molecular Genetics
Anna Ritz, Pamela L Paris, Michael M Ittmann, Colin Collins, Benjamin J Raphael
BACKGROUND: Copy number variants (CNVs), including deletions, amplifications, and other rearrangements, are common in human and cancer genomes. Copy number data from array comparative genome hybridization (aCGH) and next-generation DNA sequencing is widely used to measure copy number variants. Comparison of copy number data from multiple individuals reveals recurrent variants. Typically, the interior of a recurrent CNV is examined for genes or other loci associated with a phenotype. However, in some cases, such as gene truncations and fusion genes, the target of variant lies at the boundary of the variant...
2011: BMC Bioinformatics
Kathryn L Penney, Saumyadipta Pyne, Fredrick R Schumacher, Jennifer A Sinnott, Lorelei A Mucci, Peter L Kraft, Jing Ma, William K Oh, Tobias Kurth, Philip W Kantoff, Edward L Giovannucci, Meir J Stampfer, David J Hunter, Matthew L Freedman
BACKGROUND: A pressing clinical issue in prostate cancer is to distinguish which men will have an indolent or aggressive course of disease. Clinical variables such as Gleason grade and stage are useful predictors of lethal cancer; however, the low predictive values of the common Gleason scores, changes in grading over time, and earlier diagnosis of patients due to screening limits their clinical utility. Identifying genetic variants associated with lethal prostate cancer could inform clinical decision making...
November 2010: Cancer Epidemiology, Biomarkers & Prevention
M S Nørskov, R Frikke-Schmidt, S E Bojesen, B G Nordestgaard, S Loft, A Tybjærg-Hansen
Glutathione-S-transferase T1 (GSTT1) and GSTM1 detoxify carcinogens and thus potentially contribute to inter-individual susceptibility to cancer. We determined the ability of GST copy number variation (CNV) to predict the risk of cancer in the general population. Exact copy numbers of GSTT1 and GSTM1 were measured by real-time PCR in 10 247 individuals, of whom 2090 had cancer. In men, the cumulative incidence of prostate cancer increased and the cumulative 5-year survival decreased with decreasing GSTT1 copy numbers (trends=0...
August 2011: Pharmacogenomics Journal
Sunita R Setlur, Chen X Chen, Ruhella R Hossain, Jung Sook Ha, Vanessa E Van Doren, Birgit Stenzel, Eberhard Steiner, Derek Oldridge, Naoki Kitabayashi, Samprit Banerjee, Jin Yun Chen, Georg Schäfer, Wolfgang Horninger, Charles Lee, Mark A Rubin, Helmut Klocker, Francesca Demichelis
PURPOSE: Dihydrotestosterone (DHT) is an important factor in prostate cancer (PCA) genesis and disease progression. Given PCA's strong genetic component, we evaluated the possibility that variation in genes involved in DHT metabolism influence PCA risk. EXPERIMENTAL DESIGN: We investigated copy number variants (CNV) and single nucleotide polymorphisms (SNP). We explored associations between CNV of uridine diphospho-glucuronosyltransferase (UGT) genes from the 2B subclass, given their prostate specificity and/or involvement in steroid metabolism and PCA risk...
January 2010: Cancer Epidemiology, Biomarkers & Prevention
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