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prostate cancer genomic sequencing

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https://www.readbyqxmd.com/read/29206995/concordance-of-circulating-tumor-dna-and-matched-metastatic-tissue-biopsy-in-prostate-cancer
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/29145505/spontaneous-development-of-epstein-barr-virus-associated-human-lymphomas-in-a-prostate-cancer-xenograft-program
#9
Alberto J Taurozzi, Ramprakash Beekharry, Michelle Wantoch, Marie-Christine Labarthe, Hannah F Walker, Robert I Seed, Matthew Simms, Greta Rodrigues, James Bradford, Geertje van der Horst, Gabri van der Pluijm, Anne T Collins
Prostate cancer research is hampered by the lack of in vivo preclinical models that accurately reflect patient tumour biology and the clinical heterogeneity of human prostate cancer. To overcome these limitations we propagated and characterised a new collection of patient-derived prostate cancer xenografts. Tumour fragments from 147 unsupervised, surgical prostate samples were implanted subcutaneously into immunodeficient Rag2-/-γC-/- mice within 24 hours of surgery. Histologic and molecular characterisation of xenografts was compared with patient characteristics, including androgen-deprivation therapy, and exome sequencing...
2017: PloS One
https://www.readbyqxmd.com/read/29127096/retention-of-interstitial-genes-between-tmprss2-and-erg-is-associated-with-low-risk-prostate-cancer
#10
Stephen J Murphy, Farhad Kosari, R Jeffrey Karnes, Aqsa Nasir, Sarah H Johnson, Athanasios G Gaitatzes, James B Smadbeck, Laureano J Rangel, George Vasmatzis, John C Cheville
TMPRSS2-ERG gene fusions occur in over 50% of prostate cancers, but their impact on clinical outcomes is not well understood. Retention of interstitial genes between TMPRSS2 and ERG has been reported to influence tumor progression in an animal model. In this study, we analyzed the status of TMPRSS2-ERG fusion genes and interstitial genes in tumors from a large cohort of men treated surgically for prostate cancer, associating alterations with biochemical progression. Through whole-genome mate pair sequencing, we mapped and classified rearrangements driving ETS family gene fusions in 133 cases of very low-, low-, intermediate-, and high-risk prostate cancer from radical prostatectomy specimens...
November 10, 2017: Cancer Research
https://www.readbyqxmd.com/read/29126443/ubiquitin-c-terminal-hydrolase-isozyme-l1-is-associated-with-shelterin-complex-at-interstitial-telomeric-sites
#11
Aleksandar Ilic, Sumin Lu, Vikram Bhatia, Farhana Begum, Thomas Klonisch, Prasoon Agarwal, Wayne Xu, James R Davie
BACKGROUND: Ubiquitin C-terminal hydrolase isozyme L1 (UCHL1) is primarily expressed in neuronal cells and neuroendocrine cells and has been associated with various diseases, including many cancers. It is a multifunctional protein involved in deubiquitination, ubiquitination and ubiquitin homeostasis, but its specific roles are disputed and still generally undetermined. RESULTS: Herein, we demonstrate that UCHL1 is associated with genomic DNA in certain prostate cancer cell lines, including DU 145 cells derived from a brain metastatic site, and in HEK293T embryonic kidney cells with a neuronal lineage...
November 10, 2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/29119376/regulatory-effects-of-antitumor-agent-matrine-on-foxo-and-pi3k-akt-pathway-in-castration-resistant-prostate-cancer-cells
#12
Qi Li, Hai Huang, Zheng He, Yi Sun, Yufeng Tang, Xiaohong Shang, Chengbin Wang
We previously demonstrated that matrine could inhibit the proliferating, migrating, as well as invading processes of both PC-3 and DU145 cells. However, the underlying molecular mechanisms have not yet been clearly defined. In this study, using various techniques such as high throughput sequencing technology, bioinformatics, quantitative real-time PCR, and immunoblot analysis, we aimed to understand whether matrine serves as a novel regulator of FOXO and PI3K-AKT signaling pathway. DU145 and PC-3 cell lines were cultured for 24 h in vitro...
November 7, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/29109393/scalable-whole-exome-sequencing-of-cell-free-dna-reveals-high-concordance-with-metastatic-tumors
#13
Viktor A Adalsteinsson, Gavin Ha, Samuel S Freeman, Atish D Choudhury, Daniel G Stover, Heather A Parsons, Gregory Gydush, Sarah C Reed, Denisse Rotem, Justin Rhoades, Denis Loginov, Dimitri Livitz, Daniel Rosebrock, Ignaty Leshchiner, Jaegil Kim, Chip Stewart, Mara Rosenberg, Joshua M Francis, Cheng-Zhong Zhang, Ofir Cohen, Coyin Oh, Huiming Ding, Paz Polak, Max Lloyd, Sairah Mahmud, Karla Helvie, Margaret S Merrill, Rebecca A Santiago, Edward P O'Connor, Seong H Jeong, Rachel Leeson, Rachel M Barry, Joseph F Kramkowski, Zhenwei Zhang, Laura Polacek, Jens G Lohr, Molly Schleicher, Emily Lipscomb, Andrea Saltzman, Nelly M Oliver, Lori Marini, Adrienne G Waks, Lauren C Harshman, Sara M Tolaney, Eliezer M Van Allen, Eric P Winer, Nancy U Lin, Mari Nakabayashi, Mary-Ellen Taplin, Cory M Johannessen, Levi A Garraway, Todd R Golub, Jesse S Boehm, Nikhil Wagle, Gad Getz, J Christopher Love, Matthew Meyerson
Whole-exome sequencing of cell-free DNA (cfDNA) could enable comprehensive profiling of tumors from blood but the genome-wide concordance between cfDNA and tumor biopsies is uncertain. Here we report ichorCNA, software that quantifies tumor content in cfDNA from 0.1× coverage whole-genome sequencing data without prior knowledge of tumor mutations. We apply ichorCNA to 1439 blood samples from 520 patients with metastatic prostate or breast cancers. In the earliest tested sample for each patient, 34% of patients have ≥10% tumor-derived cfDNA, sufficient for standard coverage whole-exome sequencing...
November 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/29102647/the-transcriptional-landscape-of-radiation-treated-human-prostate-cancer-analysis-of-a-prospective-tissue-cohort
#14
Simon P Keam, Franco Caramia, Cristina Gamell, Piotr J Paul, Gisela Mir Arnau, Paul J Neeson, Scott G Williams, Ygal Haupt
PURPOSE: The resistance of prostate cancer to radiation therapy (RT) is a significant clinical issue and still largely unable to be guided by patient-specific molecular characteristics. The present study describes the gene expression changes induced in response to RT in human prostate tissue obtained from a prospective tissue acquisition study designed for radiobiology research. METHODS AND MATERIALS: A prospective cohort of 5 men with intermediate-risk and clinically localized tumors were treated with high-dose-rate brachytherapy with 2 × 10-Gy fractions...
September 25, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29101113/treatment-of-advanced-prostate-cancer-a-review-of-current-therapies-and-future-promise
#15
Semini Sumanasuriya, Johann De Bono
Despite many recent advances in the therapy for metastatic castration-resistant prostate cancer (mCRPC), the disease remains incurable, although men suffering from this disease are living considerably longer. In this review, we discuss the current treatment options available for this disease, such as taxane-based chemotherapy, the novel hormone therapies abiraterone and enzalutamide, and treatments such as radium-223 and sipuleucel-T. We also highlight the need for ongoing research in this field, because, despite numerous recent advances, the prognosis for mCRPC remains poor...
November 3, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/29101112/prostate-cancer-germline-variations-and-implications-for-screening-and-treatment
#16
Alexander Dias, Zsofia Kote-Jarai, Christos Mikropoulos, Ros Eeles
Prostate cancer (PCa) is a highly heritable disease, and rapid evolution of sequencing technologies has enabled marked progression of our understanding of its genetic inheritance. A complex polygenic model that involves common low-penetrance susceptibility alleles causing individually small but cumulatively significant risk and rarer genetic variants causing greater risk represent the current most accepted model. Through genome-wide association studies, more than 100 single-nucleotide polymorphisms (SNPs) associated with PCa risk have been identified...
November 3, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/29072143/detecting-large-deletions-at-base-pair-level-by-combining-split-read-and-paired-read-data
#17
Matthew Hayes, Jeremy S Pearson
BACKGROUND: Genomic structural variants (SV) play a significant role in the onset and progression of cancer. Genomic deletions can create oncogenic fusion genes or cause the loss of tumor suppressing gene function which can lead to tumorigenesis by downregulating these genes. Detecting these variants has clinical importance in the treatment of diseases. Furthermore, it is also clinically important to detect their breakpoint boundaries at high resolution. We have generalized the framework of a previously-published algorithm that located translocations, and we have applied that framework to develop a method to locate deletions at base pair level using next-generation sequencing data...
October 16, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/29069303/a-prospective-genome-wide-study-of-prostate-cancer-metastases-reveals-association-of-wnt-pathway-activation-and-increased-cell-cycle-proliferation-with-primary-resistance-to-abiraterone-acetate-prednisone
#18
L Wang, S M Dehm, D W Hillman, H Sicotte, W Tan, M Gormley, V Bhargava, R Jimenez, F Xie, P Yin, S Qin, F Quevedo, B A Costello, H C Pitot, T Ho, A H Bryce, Z Ye, Y Li, P Eiken, P T Vedell, P Barman, B P McMenomy, T D Atwell, R E Carlson, M Ellingson, B Eckloff, R Qin, F Ou, S N Hart, H Huang, J Jen, E D Wieben, K R Kalari, R M Weinshilboum, L Wang, M Kohli
Background: Genomic aberrations have been identified in metastatic castration-resistant prostate cancer (mCRPC), but molecular predictors of resistance to abiraterone acetate/prednisone (AA/P) treatment are not known. Patients and Methods: In a prospective clinical trial, mCRPC patients underwent whole exome sequencing (n = 82) and RNA-sequencing (n = 75) of metastatic biopsies before initiating AA/P with the objective of identifying genomic alterations associated with resistance to AA/P...
October 23, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29067547/low-levels-of-psma-expression-limit-the-utility-of-18-f-dcfpyl-pet-ct-for-imaging-urothelial-carcinoma
#19
Scott P Campbell, Alexander S Baras, Mark W Ball, Max Kates, Noah M Hahn, Trinity J Bivalacqua, Michael H Johnson, Martin G Pomper, Mohamad E Allaf, Steven P Rowe, Michael A Gorin
OBJECTIVE: To explore the clinical utility of PSMA-targeted (18)F-DCFPyL PET/CT in patients with metastatic urothelial carcinoma. METHODS: Three patients with metastatic urothelial carcinoma were imaged with (18)F-DCFPyL PET/CT. All lesions with perceptible radiotracer uptake above background were considered positive. Maximum standardized uptake values were recorded for each detected lesion and findings on (18)F-DCFPyL PET/CT were compared to those on conventional imaging studies...
October 24, 2017: Annals of Nuclear Medicine
https://www.readbyqxmd.com/read/29056275/current-and-future-applications-of-novel-immunotherapies-in-urological-oncology-a-critical-review-of-the-literature
#20
REVIEW
Berna C Özdemir, Arlene O Siefker-Radtke, Matthew T Campbell, Sumit K Subudhi
CONTEXT: Immunotherapies promote anticancer responses with varying levels of success based on the tumor type. OBJECTIVE: In this narrative review article, we searched the literature regarding immunotherapies in genitourinary malignancies to define the state of the field, explore future applications of immune checkpoint inhibitors, cytokines, vaccines, and cellular therapies in urological oncology and evaluate possible strategies to improve the selection of patients who might benefit from such approaches...
October 19, 2017: European Urology Focus
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