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prostate cancer genomic

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https://www.readbyqxmd.com/read/28528811/ability-of-a-genomic-classifier-to-predict-metastasis-and-prostate-cancer-specific-mortality-after-radiation-or-surgery-based-on-needle-biopsy-specimens
#1
Paul L Nguyen, Zaid Haddad, Ashley E Ross, Neil E Martin, Samineh Deheshi, Lucia L C Lam, Jijumon Chelliserry, Jeffrey J Tosoian, Tamara L Lotan, Daniel E Spratt, Radka S Stoyanova, Sanoj Punnen, Kaye Ong, Christine Buerki, Maria Aranes, Tyler Kolisnik, Jennifer Margrave, Kasra Yousefi, Voleak Choeurng, Elai Davicioni, Bruce J Trock, Christopher J Kane, Alan Pollack, John W Davis, Felix Y Feng, Eric A Klein
BACKGROUND: Decipher is a validated genomic classifier developed to determine the biological potential for metastasis after radical prostatectomy (RP). OBJECTIVE: To evaluate the ability of biopsy Decipher to predict metastasis and Prostate cancer-specific mortality (PCSM) in primarily intermediate- to high-risk patients treated with RP or radiation therapy (RT). DESIGN, SETTING, AND PARTICIPANTS: Two hundred and thirty-five patients treated with either RP (n=105) or RT±androgen deprivation therapy (n=130) with available genomic expression profiles generated from diagnostic biopsy specimens from seven tertiary referral centers...
May 18, 2017: European Urology
https://www.readbyqxmd.com/read/28527622/genome-wide-copy-number-analysis-reveals-candidate-gene-loci-that-confer-susceptibility-to-high-grade-prostate-cancer
#2
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
https://www.readbyqxmd.com/read/28521441/the-context-of-prostate-cancer-genomics-in-personalized-medicine
#3
Yanling Liu
Prostate cancer is one of the most common types of cancer in males. Heterogeneous genomic aberrations may lead to prostate cancer onset, progression and metastasis. This heterogeneity also contributes to the variety in cancer risk and outcomes, different drug responses and progression, observed between individual patients. Classical prognostic factors, including prostate-specific antigen, Gleason Score and clinical tumor staging, are not sufficient to portray the complexity of a clinically relevant cancer diagnosis, risk prognosis, treatment choice and therapy monitoring...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28515807/external-validation-of-the-procars-nomograms-and-comparison-of-existing-risk-stratification-tools-for-localized-prostate-cancer
#4
David Tiberi, George Rodrigues, Tom Pickles, Jim Morris, Juanita Crook, Andre-Guy Martin, Fabio Cury, Charles Catton, Himu Lukka, Andrew Warner, Daniel Taussky
INTRODUCTION: The purpose of this study was to perform a direct comparison of several existing risk-stratification tools for localized prostate cancer in terms of their ability to predict for biochemical failure-free survival (BFFS). Two large databases were used and an external validation of two recently developed nomograms on an independent cohort was also performed in this analysis. METHODS: Patients who were treated with external beam radiotherapy (EBRT) and/or brachytherapy for localized prostate cancer were selected from the multi-institutional Genitourinary Radiation Oncologists of Canada (GUROC) Prostate Cancer Risk Stratification (ProCaRS) database (n=7974) and the Centre Hospitalier de l'Université de Montréal (CHUM) validation database (n=2266)...
March 2017: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
https://www.readbyqxmd.com/read/28515422/up-regulation-and-nuclear-translocation-of-y-box-binding-protein-1-yb-1-is-linked-to-poor-prognosis-in-erg-negative-prostate-cancer
#5
Asmus Heumann, Özge Kaya, Christoph Burdelski, Claudia Hube-Magg, Martina Kluth, Dagmar S Lang, Ronald Simon, Burkhard Beyer, Imke Thederan, Guido Sauter, Jakob R Izbicki, Andreas M Luebke, Andrea Hinsch, Frank Jacobsen, Corinna Wittmer, Franziska Büscheck, Doris Höflmayer, Sarah Minner, Maria Christina Tsourlakis, Thorsten Schlomm, Waldemar Wilczak
Y-box binding protein 1 (YB-1) is an RNA and DNA binding factor with potential prognostic cancer. To evaluate the clinical impact of YB-1, a tissue microarray with 11,152 prostate cancers was analysed by immunohistochemistry. Cytoplasmic and nuclear staining was separately analysed. Cytoplasmic YB-1 was absent or weak in normal epithelium but seen in 86,3% of carcinomas. Cytoplasmic staining was weak, moderate, and strong in 29.6%, 43.7% and 13.0% of tumours and was accompanied by nuclear YB-1 staining in 32...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28515055/exome-sequencing-of-african-american-prostate-cancer-reveals-loss-of-function-erf-mutations
#6
Franklin W Huang, Juan Miguel Mosquera, Andrea Garofalo, Coyin Oh, Maria Baco, Ali Amin-Mansour, Bokang Rabasha, Samira Bahl, Stephanie A Mullane, Brian D Robinson, Saud Aldubayan, Francesca Khani, Beerinder Karir, Eejung Kim, Jeremy Chimene-Weiss, Matan Hofree, Alessandro Romanel, Joseph R Osborne, Jong Wook Kim, Gissou Azabdaftari, Anna Woloszynska-Read, Karen Sfanos, Angelo M De Marzo, Francesca Demichelis, Stacey Gabriel, Eliezer M Van Allen, Jill Mesirov, Pablo Tamayo, Mark A Rubin, Isaac J Powell, Levi A Garraway
African-American men have the highest incidence and mortality from prostate cancer. Whether a biological basis exists for this disparity remains unclear. Exome sequencing (n=102) and targeted validation (n = 90) of localized primary hormone-naïve prostate cancer in African-American men identified several gene mutations not previously observed in this context, including recurrent loss-of-function mutations in ERF, an ETS transcriptional repressor, in 5% of cases. Analysis of existing prostate cancer cohorts revealed ERF deletions in 3% of primary prostate cancers and mutations or deletions in ERF in 3-5% of lethal castration-resistant prostate cancers...
May 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28511883/a-prostate-cancer-nimbosus-genomic-instability-and-schlap1-dysregulation-underpin-aggression-of-intraductal-and-cribriform-subpathologies
#7
Melvin L K Chua, Winnie Lo, Melania Pintilie, Jure Murgic, Emilie Lalonde, Vinayak Bhandari, Osman Mahamud, Anuradha Gopalan, Charlotte F Kweldam, Geert J L H van Leenders, Esther I Verhoef, Agnes Marije Hoogland, Julie Livingstone, Alejandro Berlin, Alan Dal Pra, Alice Meng, Junyan Zhang, Michèle Orain, Valérie Picard, Hélène Hovington, Alain Bergeron, Louis Lacombe, Yves Fradet, Bernard Têtu, Victor E Reuter, Neil Fleshner, Michael Fraser, Paul C Boutros, Theodorus H van der Kwast, Robert G Bristow
BACKGROUND: Intraductal carcinoma (IDC) and cribriform architecture (CA) represent unfavorable subpathologies in localized prostate cancer. We recently showed that IDC shares a clonal ancestry with the adjacent glandular adenocarcinoma. OBJECTIVE: We investigated for the co-occurrence of "aggression" factors, genomic instability and hypoxia, and performed gene expression profiling of these tumors. DESIGN, SETTING, AND PARTICIPANTS: A total of 1325 men were treated for localized prostate cancer from four academic institutions (University Health Network, CHU de Québec-Université Laval, Memorial Sloan Kettering Cancer Center [MSKCC], and Erasmus Medical Center)...
May 13, 2017: European Urology
https://www.readbyqxmd.com/read/28511652/ing3-promotes-prostate-cancer-growth-by-activating-the-androgen-receptor
#8
Arash Nabbi, Urszula L McClurg, Subhash Thalappilly, Amal Almami, Mahsa Mobahat, Tarek A Bismar, Olivier Binda, Karl T Riabowol
BACKGROUND: The androgen receptor (AR) is a major driver of prostate cancer, and increased AR levels and co-activators of the receptor promote the development of prostate cancer. INhibitor of Growth (ING) proteins target lysine acetyltransferase or lysine deacetylase complexes to the histone H3K4Me3 mark of active transcription, to affect chromatin structure and gene expression. ING3 is a stoichiometric member of the TIP60 lysine acetyltransferase complex implicated in prostate cancer development...
May 16, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28510291/associations-between-rna-splicing-regulatory-variants-of-stemness-related-genes-and-racial-disparities-in-susceptibility-to-prostate-cancer
#9
Yanru Wang, Jennifer A Freedman, Hongliang Liu, Patricia G Moorman, Terry Hyslop, Daniel J George, Norman H Lee, Steven R Patierno, Qingyi Wei
Evidence suggests that cells with a stemness phenotype play a pivotal role in oncogenesis, and prostate cells exhibiting this phenotype have been identified. We used two genome-wide association study (GWAS) datasets of African descendants, from the Multiethnic/Minority Cohort Study of Diet and Cancer (MEC) and the Ghana Prostate Study, as well as two GWAS datasets of non-Hispanic whites, from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and the Breast and Prostate Cancer Cohort Consortium (BPC3), to analyze the associations between genetic variants of stemness-related genes and racial disparities in susceptibility to prostate cancer...
May 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28504904/application-of-panel-based-tests-for-inherited-risk-of-cancer
#10
Payal D Shah, Katherine L Nathanson
Next-generation or massively parallel sequencing has transformed the landscape of genetic testing for cancer susceptibility. Panel-based genetic tests evaluate multiple genes simultaneously and rapidly. Because these tests are frequently offered in clinical settings, understanding their clinical validity and utility is critical. When evaluating the inherited risk of breast and ovarian cancers, panel-based tests provide incremental benefit compared with BRCA1/2 genetic testing. For inherited risk of other cancers, such as colon cancer and pheochromocytoma-paraganglioma, the clinical utility and yield of panel-based testing are higher; in fact, simultaneous evaluation of multiple genes has been the historical standard for these diseases...
May 15, 2017: Annual Review of Genomics and Human Genetics
https://www.readbyqxmd.com/read/28501990/tumor-staging-and-grading-a-primer
#11
Stacy M Telloni
Cancer staging and grading are used to predict the clinical behavior of malignancies, establish appropriate therapies, and facilitate exchange of precise information between clinicians. The internationally accepted criterion for cancer staging, the tumor-node-metastasis (TNM) system, includes: (1) tumor size and local growth (T), (2) extent of lymph node metastases (N), and (3) occurrence of distant metastases (M). Clinical stage is established before initiation of therapy and is determined by physical examination, laboratory findings, and imaging studies...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28496006/gene-expression-signature-of-gleason-score-is-associated-with-prostate-cancer-outcomes-in-a-radical-prostatectomy-cohort
#12
Min A Jhun, Milan S Geybels, Jonathan L Wright, Suzanne Kolb, Craig April, Marina Bibikova, Elaine A Ostrander, Jian-Bing Fan, Ziding Feng, Janet L Stanford
Prostate cancer (PCa) is a leading cause of cancer-related mortality worldwide. Gleason score (GS) is one of the best predictors of PCa aggressiveness, but additional tumor biomarkers may improve its prognostic accuracy. We developed a gene expression signature of GS to enhance the prediction of PCa outcomes. Elastic net was used to construct a gene expression signature by contrasting GS 8-10 vs. ≤6 tumors in The Cancer Genome Atlas (TCGA) dataset. The constructed signature was then evaluated for its ability to predict recurrence and metastatic-lethal (ML) progression in a Fred Hutchinson (FH) patient cohort (N=408; NRecurrence=109; NMLprogression=27)...
April 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28487881/whole-genome-sequencing-identifies-homozygous-brca2-deletion-guiding-treatment-in-dedifferentiated-prostate-cancer
#13
Karin Purshouse, Anna Schuh, Benjamin P Fairfax, Sam Knight, Pavlos Antoniou, Helene Dreau, Niko Popitsch, Kevin Gatter, Ian Roberts, Lisa Browning, Zoe Traill, David Kerr, Clare Verrill, Mark Tuthill, Jenny C Taylor, Andrew Protheroe
Whole-genome sequencing (WGS) has transformed the understanding of the genetic drivers of cancer and is increasingly being used in cancer medicine to identify personalized therapies. Here we describe a case in which the application of WGS identified a tumoral BRCA2 deletion in a patient with aggressive dedifferentiated prostate cancer that was repeat-biopsied after disease progression. This would not have been detected by standard BRCA testing, and it led to additional treatment with a maintenance poly ADP ribose polymerase (PARP) inhibitor following platinum-based chemotherapy...
May 2017: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/28486497/towards-decision-making-using-individualized-risk-estimates-for-personalized-medicine-a-systematic-review-of-genomic-classifiers-of-solid-tumors
#14
Daniel M Trifiletti, Vanessa N Sturz, Timothy N Showalter, Jennifer M Lobo
Recent advances in the understanding of the genetic underpinnings of cancer offer the promise to customize cancer treatments to the individual through the use of genomic classifiers (GCs). At present, routine clinical utilization of GCs is uncommon and their current scope and status, in a broad sense, are unknown. As part of a registered review (PROSPERO 2014:CRD42014013371), we systematically reviewed the literature evaluating the utility of commercially available GCs by searching Ovid Medline (PubMed), EMBASE, the Cochrane Database of Systematic Reviews, and CINAHL on September 2, 2014...
2017: PloS One
https://www.readbyqxmd.com/read/28483704/genome-wide-analysis-of-ar-binding-and-comparison-with-transcript-expression-in-primary-human-fetal-prostate-fibroblasts-and-cancer-associated-fibroblasts
#15
REVIEW
Claire Nash, Nadia Boufaied, Ian G Mills, Omar E Franco, Simon W Hayward, Axel A Thomson
The androgen receptor (AR) is a transcription factor, and key regulator of prostate development and cancer, which has discrete functions in stromal versus epithelial cells. AR expressed in mesenchyme is necessary and sufficient for prostate development while loss of stromal AR is predictive of prostate cancer progression. Many studies have characterized genome-wide binding of AR in prostate tumour cells but none have used primary mesenchyme or stroma. We applied ChIPseq to identify genomic AR binding sites in primary human fetal prostate fibroblasts and patient derived cancer associated fibroblasts, as well as the WPMY1 cell line overexpressing AR...
May 5, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28477422/prostate-cancer-molecular-profiling-the-achille-s-heel-for-the-implementation-of-precision-medicine
#16
REVIEW
Eliane Gouvêa de Oliveira Barros, Pedro Nicolau-Neto, Nathalia Meireles Da Costa, Luís Felipe Ribeiro Pinto, Antonio Palumbo Jr, Luiz Eurico Nasciutti
Cancer has been mainly treated by traditional therapeutic approaches which do not consider the human genetic diversity and present limitations, probably as a consequence of a poor knowledge of both patient's genetic background and tumor biology. Due to genome project conclusion and large scale gene analyses emergence, the therapeutic management of several prevalent and aggressive tumors has dramatically improved and represents the closest examples of a precision medicine intervention in this field. Nonetheless, prostate cancer (PCa) remains as a challenge to personalized medicine implementation, probably due to its notorious heterogeneous molecular profile...
May 6, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28472770/modeling-african-american-prostate-adenocarcinoma-by-inducing-defined-genetic-alterations-in-organoids
#17
Kenji Unno, Meejeon Roh, Young A Yoo, Yousef Al-Shraideh, Lu Wang, Larisa Nonn, Sarki A Abdulkadir
Genomic studies are rapidly identifying genetic alterations in human cancer, but functional validation of such alterations has been slow. Here, using human prostate cancer as a model, we have assessed the feasibility of engineering defined genetic alterations in well-known cancer driver genes to transform benign prostate epithelial organoids derived from African American men. Benign human prostate organoids were transduced with lentiviruses expressing MYC, shPTEN, shTP53 and AR, alone and in various combinations, to recapitulate prostate cancer development...
April 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28471803/search-for-genetic-factor-association-with-cancer-free-prostate-specific-antigen-level-elevation-on-the-basis-of-a-genome-wide-association-study-in-the-korean-population
#18
Eun Kyung Choe, Young Lee, Jeong Yeon Cho, Seung Ho Choi, Boram Park, Jong-Eun Lee, Eun Young Cho
We investigated the genetic markers associated with elevated serum prostate-specific antigen (sPSA) levels to improve the predictive power of sPSA in screening for prostate cancer. A genome-wide association study was carried out among 4124 healthy Korean male adults using the Affymetrix Axiom Customized Biobank Genotyping Arrays for sPSA levels. A subgroup analysis for increased sPSA levels who underwent a prostate biopsy (n=64) was also carried out. We detected 11 single nucleotide polymorphisms (SNPs) near the Solute carrier family 45member 3, AGAP7P, MSMB, LOC101929917, and KLK3 genes associated with sPSA levels...
May 3, 2017: European Journal of Cancer Prevention
https://www.readbyqxmd.com/read/28471706/can-genomic-data-guide-the-postoperative-management-of-prostate-cancer
#19
Rahul R Parikh, Isaac Yi Kim
No abstract text is available yet for this article.
May 4, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28469398/an-integrative-genomics-approach-for-associating-genome-wide-association-studies-information-with-localized-and-metastatic-prostate-cancer-phenotypes
#20
Chindo Hicks, Ritika Ramani, Oliver Sartor, Ritu Bhalla, Lucio Miele, Zodwa Dlamini, Njabulo Gumede
High-throughput genotyping has enabled discovery of genetic variants associated with an increased risk of developing prostate cancer using genome-wide association studies (GWAS). The goal of this study was to associate GWAS information of patients with primary organ-confined and metastatic prostate cancer using gene expression data and to identify molecular networks and biological pathways enriched for genetic susceptibility variants involved in the 2 disease states. The analysis revealed gene signatures for the 2 disease states and a gene signature distinguishing the 2 patient groups...
2017: Biomarker Insights
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