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prostate cancer genomic sequencing

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https://www.readbyqxmd.com/read/29429977/zfx-acts-as-a-transcriptional-activator-in-multiple-types-of-human-tumors-by-binding-downstream-of-transcription-start-sites-at-the-majority-of-cpg-island-promoters
#1
Suhn Kyong Rhie, Lijun Yao, Zhifei Luo, Heather Witt, Shannon Schreiner, Yu Guo, Andrew A Perez, Peggy J Farnham
High expression of the transcription factor ZFX is correlated with proliferation, tumorigenesis, and patient survival in multiple types of human cancers. However, the mechanism by which ZFX influences transcriptional regulation has not been determined. We performed ChIP-seq in four cancer cell lines (representing kidney, colon, prostate, and breast cancers) to identify ZFX binding sites throughout the human genome. We identified ~9,000 ZFX binding sites and found that the majority of the sites are in CpG island promoters...
February 2, 2018: Genome Research
https://www.readbyqxmd.com/read/29398457/genomic-heterogeneity-within-individual-prostate-cancer-foci-impacts-predictive-biomarkers-of-targeted-therapy
#2
David J VanderWeele, Richard Finney, Kotoe Katayama, Marc Gillard, Gladell Paner, Seiya Imoto, Rui Yamaguchi, David Wheeler, Justin Lack, Maggie Cam, Andrea Pontier, Yen Thi Minh Nguyen, Kazuhiro Maejima, Aya Sasaki-Oku, Kaoru Nakano, Hiroko Tanaka, Donald Vander Griend, Michiaki Kubo, Mark J Ratain, Satoru Miyano, Hidewaki Nakagawa
BACKGROUND: Most lethal prostate cancers progress from relapse of aggressive primary disease. Recently, the most significant advances in survival benefit from systemic therapy have come from moving the administration of therapy to an earlier disease state. There is movement toward using biomarkers from the intraprostatic index lesion to guide early systemic therapy. OBJECTIVE: To determine the genomic heterogeneity, including the heterogeneity of predictive biomarkers, within the index focus of treatment-naïve prostate cancer...
February 1, 2018: European Urology Focus
https://www.readbyqxmd.com/read/29368341/intraductal-ductal-histology-and-lymphovascular-invasion-are-associated-with-germline-dna-repair-gene-mutations-in-prostate-cancer
#3
Pedro Isaacsson Velho, John L Silberstein, Mark C Markowski, Jun Luo, Tamara L Lotan, William B Isaacs, Emmanuel S Antonarakis
BACKGROUND: Germline mutations in genes mediating DNA repair are common in men with recurrent and advanced prostate cancer, and their presence may alter prognosis and management. We aimed to define pathological and clinical characteristics associated with germline DNA-repair gene mutations, to facilitate selection of patients for germline testing. METHODS: We retrospectively evaluated 150 unselected patients with recurrent or metastatic prostate cancer who were offered germline genetic testing by a single oncologist using a clinical-grade assay (Color Genomics)...
January 25, 2018: Prostate
https://www.readbyqxmd.com/read/29367197/circulating-tumor-dna-genomics-correlate-with-resistance-to-abiraterone-and-enzalutamide-in-prostate-cancer
#4
Matti Annala, Gillian Vandekerkhove, Daniel Khalaf, Sinja Taavitsainen, Kevin Beja, Evan W Warner, Katherine Sunderland, Christian Kollmannsberger, Bernhard J Eigl, Daygen Finch, Conrad D Oja, Joanna Vergidis, Muhammad Zulfiqar, Arun A Azad, Matti Nykter, Martin E Gleave, Alexander W Wyatt, Kim N Chi
Primary resistance to androgen receptor (AR) directed therapies in metastatic castration-resistant prostate cancer (mCRPC) is poorly understood. We randomized 202 treatment-naive mCRPC patients to abiraterone or enzalutamide, and performed whole exome and deep targeted 72-gene sequencing of plasma cell-free DNA prior to therapy. For these agents, which have never been directly compared, time to progression was similar. Defects in BRCA2 and ATM were strongly associated with poor clinical outcomes independently of clinical prognostic factors and circulating tumor DNA abundance...
January 24, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29344347/epigenetic-alterations-in-tramp-mice-epigenome-dna-methylation-profiling-using-medip-seq
#5
Wenji Li, Ying Huang, Davit Sargsyan, Tin Oo Khor, Yue Guo, Limin Shu, Anne Yuqing Yang, Chengyue Zhang, Ximena Paredes-Gonzalez, Michael Verzi, Ronald P Hart, Ah-Ng Kong
Purpose: We investigated the genomic DNA methylation profile of prostate cancer in transgenic adenocarcinoma of the mouse prostate (TRAMP) cancer model and to analyze the crosstalk among targeted genes and the related functional pathways. Methods: Prostate DNA samples from 24-week-old TRAMP and C57BL/6 male mice were isolated. The DNA methylation profiles were analyzed by methylated DNA immunoprecipitation (MeDIP) followed by next-generation sequencing (MeDIP-seq)...
2018: Cell & Bioscience
https://www.readbyqxmd.com/read/29339834/use-of-multicolor-fluorescence-in-situ-hybridization-to-detect-deletions-in-clinical-tissue-sections
#6
REVIEW
Maisa Yoshimoto, Olga Ludkovski, Jennifer Good, Ciro Pereira, Robert J Gooding, Jean McGowan-Jordan, Alexander Boag, Andrew Evans, Ming-Sound Tsao, Paulo Nuin, Jeremy A Squire
A variety of laboratory methods are available for the detection of deletions of tumor suppressor genes and losses of their proteins. The clinical utility of fluorescence in situ hybridization (FISH) for the identification of deletions of tumor suppressor genes has previously been limited by difficulties in the interpretation of FISH signal patterns. The first deletion FISH assays using formalin-fixed paraffin-embedded tissue sections had to deal with a significant background level of signal losses affecting nuclei that are truncated by the cutting process of slide preparation...
January 16, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29324665/genome-wide-methylation-patterns-in-androgen-independent-prostate-cancer-cells-a-comprehensive-analysis-combining-medip-bisulfite-rna-and-microrna-sequencing-data
#7
Yumin Wang, Tingting Qin, Wangqiang Hu, Binghua Chen, Meijie Dai, Gang Xu
This study aimed to investigate the mechanisms underlying the development of the androgen-independent phenotype in prostate cancer. Methylation patterns were detected in androgen-independent and androgen-dependent lymph node carcinoma of the prostate (LNCaP) prostate carcinoma cells based on methylated DNA immunoprecipitation-bisulfite sequencing data and differentially methylated regions (DMRs) were identified. Differentially expressed genes (DEGs) and micro RNAs (miRNAs) with DMRs (named MDEGs and MDEmiRNAs) were identified by combining transcriptome and methylation data, and transcription factor (TF)-DEGs with DMRs in promoter (PMDEGs) and MDEmiRNA-MDEGs networks were constructed...
January 11, 2018: Genes
https://www.readbyqxmd.com/read/29302046/p53-status-in-the-primary-tumor-predicts-efficacy-of-subsequent-abiraterone-and-enzalutamide-in-castration-resistant-prostate-cancer
#8
Benjamin L Maughan, Liana B Guedes, Kenneth Boucher, Gaurav Rajoria, Zach Liu, Szczepan Klimek, Roberto Zoino, Emmanuel S Antonarakis, Tamara L Lotan
BACKGROUND: We tested whether tissue-based analysis of p53 and PTEN genomic status in primary tumors is predictive for subsequent sensitivity to abiraterone and enzalutamide in castration-resistant prostate cancer (CRPC). METHODS: We performed a retrospective analysis of 309 consecutive patients with CRPC treated with abiraterone or enzalutamide. Of these, 101 men (33%) had available primary tumor tissue for analysis. We screened for deleterious TP53 missense mutations and PTEN deletions using genetically validated immunohistochemical assays for nuclear accumulation of p53 protein and PTEN protein loss, with sequencing confirmation of TP53 mutations in a subset...
January 4, 2018: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/29297493/the-genomics-of-prostate-cancer-emerging-understanding-with-technologic-advances
#9
Mark A Rubin, Francesca Demichelis
With the advent of next-generation sequencing technologies and large whole-exome and genome studies in prostate and other cancers, our understanding of the landscape of genomic alterations has dramatically been refined. In additional to well-known alterations in genomic regions involving 8p, 8q, 10q23, common ETS translocations and androgen receptor amplifications, newer technology have uncovered recurrent mutations in SPOP, FOXA1, MED12, IDH and complex large scale genomic alterations (eg, chromoplexy). This review surveys the enhanced landscape of genomic alterations in clinically localized and advanced prostate cancer...
January 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29247555/the-triterpenoid-corosolic-acid-blocks-transformation-and-epigenetically-reactivates-nrf2-in-tramp-c1-prostate-cells
#10
Jie Yang, Renyi Wu, Wenji Li, Linbo Gao, Yuqing Yang, Ping Li, Ah-Ng Kong
Corosolic acid (CRA) is found in various plants and has been used as a health food supplement worldwide. Although it has been reported that CRA exhibits significant anticancer activity, the effect of this compound on prostate cancer remains unknown. In this study, we investigated the effect of CRA on cellular transformation and the reactivation of nuclear factor erythroid 2-related factor 2 (Nrf2) through epigenetic regulation in TRAMP-C1 prostate cells. Specifically, we found that CRA inhibited anchorage-independent growth of prostate cancer TRAMP-C1 cells but not Nrf2 knockout prostate cancer TRAMP-C1 cells...
December 16, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29229583/integrative-genomic-analysis-of-coincident-cancer-foci-implicates-ctnnb1-and-pten-alterations-in-ductal-prostate-cancer
#11
Marc Gillard, Justin Lack, Andrea Pontier, Divya Gandla, David Hatcher, Adam G Sowalsky, Jose Rodriguez-Nieves, Donald Vander Griend, Gladell Paner, David VanderWeele
BACKGROUND: Ductal adenocarcinoma of the prostate is an aggressive subtype, with high rates of biochemical recurrence and overall poor prognosis. It is frequently found coincident with conventional acinar adenocarcinoma. The genomic features driving evolution to its ductal histology and the biology associated with its poor prognosis remain unknown. OBJECTIVE: To characterize genomic features distinguishing ductal adenocarcinoma from coincident acinar adenocarcinoma foci from the same patient...
December 8, 2017: European Urology Focus
https://www.readbyqxmd.com/read/29228771/curcumin-derivative-epigenetically-reactivates-nrf2-antioxidative-stress-signaling-in-mouse-prostate-cancer-tramp-c1-cells
#12
Wenji Li, Zheng-Yuan Su, Yue Guo, Chengyue Zhang, RenYi Wu, Linbo Gao, Xi Zheng, Zhi-Yun Du, Kun Zhang, Ah-Ng Kong
The carcinogenesis of prostate cancer (PCa) in TRAMP model is highly correlated with hypermethylation in the promoter region of Nrf2 and the accompanying reduced transcription of Nrf2 and its regulated detoxifying genes. We aimed to investigate the effects of (3E,5E)-3,5-Bis(3,4,5-trimethoxybenzylidene) -tetrahydrothiopyran-4-one (F10) and (3E,5E)-3,5-Bis(3,4,5-trimethoxybenzylidene) -tetrahydropyran-4-one (E10), two synthetic curcumin derivatives, on restoring Nrf2 activity in TRAMP C1 cells. HepG2-C8 cells transfected with an antioxidant-response element (ARE)-luciferase vector were treated with F10, E10, curcumin and sulforaphane (SFN) to compare their effects on Nrf2-ARE pathways...
December 11, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/29206995/concordance-of-circulating-tumor-dna-and-matched-metastatic-tissue-biopsy-in-prostate-cancer
#13
Alexander W Wyatt, Matti Annala, Rahul Aggarwal, Kevin Beja, Felix Feng, Jack Youngren, Adam Foye, Paul Lloyd, Matti Nykter, Tomasz M Beer, Joshi J Alumkal, George V Thomas, Robert E Reiter, Matthew B Rettig, Christopher P Evans, Allen C Gao, Kim N Chi, Eric J Small, Martin E Gleave
Background: Real-time knowledge of the somatic genome can influence management of patients with metastatic castration-resistant prostate cancer (mCRPC). While routine metastatic tissue biopsy is challenging in mCRPC, plasma circulating tumor DNA (ctDNA) has emerged as a minimally invasive tool to sample the tumor genome. However, no systematic comparisons of matched "liquid" and "solid" biopsies have been performed that would enable ctDNA profiling to replace the need for direct tissue sampling...
December 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29201018/prevalence-of-flp-pili-encoding-plasmids-in-cutibacterium-acnes-isolates-obtained-from-prostatic-tissue
#14
Sabina Davidsson, Jessica Carlsson, Paula Mölling, Natyra Gashi, Ove Andrén, Swen-Olof Andersson, Elzbieta Brzuszkiewicz, Anja Poehlein, Munir A Al-Zeer, Volker Brinkmann, Carsten Scavenius, Seven Nazipi, Bo Söderquist, Holger Brüggemann
Inflammation is one of the hallmarks of prostate cancer. The origin of inflammation is unknown, but microbial infections are suspected to play a role. In previous studies, the Gram-positive, low virulent bacterium Cutibacterium (formerly Propionibacterium) acnes was frequently isolated from prostatic tissue. It is unclear if the presence of the bacterium represents a true infection or a contamination. Here we investigated Cutibacterium acnes type II, also called subspecies defendens, which is the most prevalent type among prostatic C...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29196557/selexglm-differentiates-androgen-and-glucocorticoid-receptor-dna-binding-preference-over-an-extended-binding-site
#15
Liyang Zhang, Gabriella D Martini, H Tomas Rube, Judith F Kribelbauer, Chaitanya Rastogi, Vincent D FitzPatrick, Jon C Houtman, Harmen J Bussemaker, Miles A Pufall
The DNA-binding interfaces of the androgen (AR) and glucocorticoid (GR) receptors are virtually identical, yet these transcription factors share only about a third of their genomic binding sites and regulate similarly distinct sets of target genes. To address this paradox, we determined the intrinsic specificities of the AR and GR DNA binding domains using a refined version of SELEX-seq. We developed an algorithm, SelexGLM, that quantifies binding specificity over a large (31 bp) binding-site by iteratively fitting a feature-based generalized linear model to SELEX probe counts...
December 1, 2017: Genome Research
https://www.readbyqxmd.com/read/29181411/rna-seq-based-transcription-characterization-of-fusion-breakpoints-as-a-potential-estimator-for-its-oncogenic-potential
#16
Jian-Lei Gu, Morris Chukhman, Yao Lu, Cong Liu, Shi-Yi Liu, Hui Lu
Based on high-throughput sequencing technology, the detection of gene fusions is no longer a big challenge but estimating the oncogenic potential of fusion genes remains challenging. Recent studies successfully applied machine learning methods and gene structural and functional features of fusion mutation to predict their oncogenic potentials. However, the transcription characterizations features of fusion genes have not yet been studied. In this study, based on the clonal evolution theory, we hypothesized that a fusion gene is more likely to be an oncogenic genomic alteration, if the neoplastic cells harboring this fusion mutation have larger clonal size than other neoplastic cells in a tumor...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29180472/utility-of-single-cell-genomics-in-diagnostic-evaluation-of-prostate-cancer
#17
Joan Alexander, Jude Kendall, Jean McIndoo, Linda Rodgers, Robert Aboukhalil, Dan Levy, Asya Stepansky, Guoli Sun, Lubomir Chobadjiev, Michael Riggs, Hilary Cox, Inessa Hakker, Dawid G Nowak, Juliana Laze, Elton Llukani, Abhishek Srivastava, Siobhan Gruschow, Shalini Singh Yadav, Brian D Robinson, Gurinder Atwal, Lloyd C Trotman, Herbert Lepor, James B Hicks, Michael Wigler, Alex Krasnitz
A distinction between indolent and aggressive disease is a major challenge in diagnostics of prostate cancer. As genetic heterogeneity and complexity may influence clinical outcome, we have initiated studies on single tumor cell genomics. In this study, we demonstrate that sparse DNA sequencing of single cell nuclei from prostate core biopsies is a rich source of quantitative parameters for evaluating neoplastic growth and aggressiveness. These include the presence of clonal populations, the phylogenetic structure of those populations, the degree of the complexity of copy number changes in those populations, and measures of the proportion of cells with clonal copy number signatures...
November 27, 2017: Cancer Research
https://www.readbyqxmd.com/read/29163793/rapid-ultra-low-coverage-copy-number-profiling-of-cell-free-dna-as-a-precision-oncology-screening-strategy
#18
Daniel H Hovelson, Chia-Jen Liu, Yugang Wang, Qing Kang, James Henderson, Amy Gursky, Scott Brockman, Nithya Ramnath, John C Krauss, Moshe Talpaz, Malathi Kandarpa, Rashmi Chugh, Missy Tuck, Kirk Herman, Catherine S Grasso, Michael J Quist, Felix Y Feng, Christine Haakenson, John Langmore, Emmanuel Kamberov, Tim Tesmer, Hatim Husain, Robert J Lonigro, Dan Robinson, David C Smith, Ajjai S Alva, Maha H Hussain, Arul M Chinnaiyan, Muneesh Tewari, Ryan E Mills, Todd M Morgan, Scott A Tomlins
Current cell-free DNA (cfDNA) next generation sequencing (NGS) precision oncology workflows are typically limited to targeted and/or disease-specific applications. In advanced cancer, disease burden and cfDNA tumor content are often elevated, yielding unique precision oncology opportunities. We sought to demonstrate the utility of a pan-cancer, rapid, inexpensive, whole genome NGS of cfDNA approach (PRINCe) as a precision oncology screening strategy via ultra-low coverage (~0.01x) tumor content determination through genome-wide copy number alteration (CNA) profiling...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29151363/functional-assessment-of-human-enhancer-activities-using-whole-genome-starr-sequencing
#19
Yuwen Liu, Shan Yu, Vineet K Dhiman, Tonya Brunetti, Heather Eckart, Kevin P White
BACKGROUND: Genome-wide quantification of enhancer activity in the human genome has proven to be a challenging problem. Recent efforts have led to the development of powerful tools for enhancer quantification. However, because of genome size and complexity, these tools have yet to be applied to the whole human genome. RESULTS:  In the current study, we use a human prostate cancer cell line, LNCaP as a model to perform whole human genome STARR-seq (WHG-STARR-seq) to reliably obtain an assessment of enhancer activity...
November 20, 2017: Genome Biology
https://www.readbyqxmd.com/read/29149895/novel-insights-into-chromosomal-conformations-in-cancer
#20
REVIEW
Ruobing Jia, Peiwei Chai, He Zhang, Xianqun Fan
Exploring gene function is critical for understanding the complexity of life. DNA sequences and the three-dimensional organization of chromatin (chromosomal interactions) are considered enigmatic factors underlying gene function, and interactions between two distant fragments can regulate transactivation activity via mediator proteins. Thus, a series of chromosome conformation capture techniques have been developed, including chromosome conformation capture (3C), circular chromosome conformation capture (4C), chromosome conformation capture carbon copy (5C), and high-resolution chromosome conformation capture (Hi-C)...
November 17, 2017: Molecular Cancer
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