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prostate cancer genomic sequencing

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https://www.readbyqxmd.com/read/29023722/prevalence-and-clonality-of-synchronous-primary-carcinomas-in-the-bladder-and-prostate
#1
Ying Jing, Ruiyun Zhang, Pengfei Ma, Mei-Chun Cai, Guanglei Zhuang, Haige Chen
Incidental prostate adenocarcinoma (IPCa) has been frequently discovered during postoperative histopathological evaluation of radical cystoprostatectomy specimens in patients with bladder cancer (BCa). However, there is currently no conclusive study addressing the clinical significance of IPCa and the clonal relatedness of IPCa and BCa. Here, we performed a retrospective single-center review of 919 BCa cases and an additional meta-analysis including a total of 19,868 individuals who underwent radical cystectomy for bladder cancer...
October 11, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28984675/feasibility-of-prostate-paxgene-fixation-for-molecular-research-and-diagnostic-surgical-pathology-comparison-of-matched-fresh-frozen-ffpe-and-pfpe-tissues
#2
Gunilla Högnäs, Kati Kivinummi, Heini M L Kallio, Reija Hieta, Pekka Ruusuvuori, Antti Koskenalho, Juha Kesseli, Teuvo L J Tammela, Jarno Riikonen, Joanna Ilvesaro, Saara Kares, Pasi P Hirvikoski, Marita Laurila, Tuomas Mirtti, Matti Nykter, Paula M Kujala, Tapio Visakorpi, Teemu Tolonen, G Steven Bova
Advances in prostate cancer biology and diagnostics are dependent upon high-fidelity integration of clinical, histomorphologic, and molecular phenotypic findings. In this study, we compared fresh frozen, formalin-fixed paraffin-embedded (FFPE), and PAXgene-fixed paraffin-embedded (PFPE) tissue preparation methods in radical prostatectomy prostate tissue from 36 patients and performed a preliminary test of feasibility of using PFPE tissue in routine prostate surgical pathology diagnostic assessment. In addition to comparing histology, immunohistochemistry, and general measures of DNA and RNA integrity in each fixation method, we performed functional tests of DNA and RNA quality, including targeted Miseq RNA and DNA sequencing, and implemented methods to relate DNA and RNA yield and quality to quantified DNA and RNA picogram nuclear content in each tissue volume studied...
October 3, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28984647/functional-genomics-of-stromal-cells-in-chronic-inflammatory-diseases
#3
Kamil Slowikowski, Kevin Wei, Michael B Brenner, Soumya Raychaudhuri
PURPOSE OF REVIEW: Stroma is a broad term referring to the connective tissue matrix in which other cells reside. It is composed of diverse cell types with functions such as extracellular matrix maintenance, blood and lymph vessel development, and effector cell recruitment. The tissue microenvironment is determined by the molecular characteristics and relative abundances of different stromal cells such as fibroblasts, endothelial cells, pericytes, and mesenchymal precursor cells. Stromal cell heterogeneity is explained by embryonic developmental lineage, stages of differentiation to other cell types, and activation states...
October 4, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28984195/md-miner-a-network-based-approach-for-personalized-drug-repositioning
#4
Haoyang Wu, Elise Miller, Denethi Wijegunawardana, Kelly Regan, Philip R O Payne, Fuhai Li
BACKGROUND: Due to advances in next generation sequencing technologies and corresponding reductions in cost, it is now attainable to investigate genome-wide gene expression and variants at a patient-level, so as to better understand and anticipate heterogeneous responses to therapy. Consequently, it is feasible to inform personalized drug treatment decisions using personal genomics data. However, these efforts are limited due to a lack of reliable computational approaches for predicting effective drugs for individual patients...
October 3, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28961847/intratumoural-evolutionary-landscape-of-high-risk-prostate-cancer-the-progeny-study-of-genomic-and-immune-parameters
#5
M Linch, G Goh, C Hiley, Y Shanmugabavan, N McGranahan, A Rowan, Y N S Wong, H King, A Furness, A Freeman, J Linares, A Akarca, J Herrero, R Rosenthal, N Harder, G Schmidt, G A Wilson, N J Birkbak, R Mitter, S Dentro, P Cathcart, M Arya, E Johnston, R Scott, M Hung, M Emberton, G Attard, Z Szallasi, S Punwani, S A Quezada, T Marafioti, M Gerlinger, H U Ahmed, C Swanton
Background: Intratumoural heterogeneity (ITH) is well recognised in prostate cancer (PC), but its role in high-risk disease is uncertain. A prospective, single-arm, translational study using targeted multiregion prostate biopsies was carried out to study genomic and T-cell ITH in clinically high-risk PC aiming to identify drivers and potential therapeutic strategies. Patients and methods: Forty-nine men with elevated prostate-specific antigen and multiparametric-magnetic resonance imaging detected PC underwent image-guided multiregion transperineal biopsy...
October 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28958406/clinical-utility-of-emerging-liquid-biomarkers-in-advanced-prostate-cancer
#6
REVIEW
Gillian Vandekerkhove, Kim N Chi, Alexander W Wyatt
The therapeutic landscape of advanced prostate cancer (PCa) has rapidly expanded in recent years. Despite significant improvements in patient overall survival, it remains challenging to determine the optimal therapy and sequence of therapies for individual patients. The development of molecular biomarkers will be key for patient stratification, and for monitoring response and resistance to therapy. In this context, minimally-invasive blood-based "liquid" biopsies are attractive as a practical surrogate for solid tumor tissue, providing a window into metastatic disease...
August 25, 2017: Cancer Genetics
https://www.readbyqxmd.com/read/28954787/mutational-analysis-of-gene-fusions-predicts-novel-mhc-class-i-restricted-t-cell-epitopes-immune-signatures-in-a-subset-of-prostate-cancer
#7
Jennifer L Kalina, David S Neilson, Yen-Yi Lin, Phineas T Hamilton, Alexandra Paige Comber, Emma M H Loy, S Cenk Sahinalp, Colin C Collins, Faraz Hach, Julian J Lum
PURPOSE: Gene fusions are frequently found in prostate cancer and may result in the formation of unique chimeric amino acid sequences (CASQs) that span the breakpoint of two fused gene products. This study evaluated the potential for fusion-derived CASQs to be a source of tumor neoepitopes, and determined their relationship to patterns of immune signatures in prostate cancer patients Experimental Design: A computational strategy was used to identify CASQs and their corresponding predicted MHC class I epitopes using RNA-Seq data from The Cancer Genome Atlas of prostate tumors...
September 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28945760/appraising-the-relevance-of-dna-copy-number-loss-and-gain-in-prostate-cancer-using-whole-genome-dna-sequence-data
#8
Niedzica Camacho, Peter Van Loo, Sandra Edwards, Jonathan D Kay, Lucy Matthews, Kerstin Haase, Jeremy Clark, Nening Dennis, Sarah Thomas, Barbara Kremeyer, Jorge Zamora, Adam P Butler, Gunes Gundem, Sue Merson, Hayley Luxton, Steve Hawkins, Mohammed Ghori, Luke Marsden, Adam Lambert, Katalin Karaszi, Gill Pelvender, Charlie E Massie, Zsofia Kote-Jarai, Keiran Raine, David Jones, William J Howat, Steven Hazell, Naomi Livni, Cyril Fisher, Christopher Ogden, Pardeep Kumar, Alan Thompson, David Nicol, Erik Mayer, Tim Dudderidge, Yongwei Yu, Hongwei Zhang, Nimish C Shah, Vincent J Gnanapragasam, William Isaacs, Tapio Visakorpi, Freddie Hamdy, Dan Berney, Clare Verrill, Anne Y Warren, David C Wedge, Andrew G Lynch, Christopher S Foster, Yong Jie Lu, G Steven Bova, Hayley C Whitaker, Ultan McDermott, David E Neal, Rosalind Eeles, Colin S Cooper, Daniel S Brewer
A variety of models have been proposed to explain regions of recurrent somatic copy number alteration (SCNA) in human cancer. Our study employs Whole Genome DNA Sequence (WGS) data from tumor samples (n = 103) to comprehensively assess the role of the Knudson two hit genetic model in SCNA generation in prostate cancer. 64 recurrent regions of loss and gain were detected, of which 28 were novel, including regions of loss with more than 15% frequency at Chr4p15.2-p15.1 (15.53%), Chr6q27 (16.50%) and Chr18q12...
September 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28939825/mitochondrial-mutations-drive-prostate-cancer-aggression
#9
Julia F Hopkins, Veronica Y Sabelnykova, Joachim Weischenfeldt, Ronald Simon, Jennifer A Aguiar, Rached Alkallas, Lawrence E Heisler, Junyan Zhang, John D Watson, Melvin L K Chua, Michael Fraser, Francesco Favero, Chris Lawerenz, Christoph Plass, Guido Sauter, John D McPherson, Theodorus van der Kwast, Jan Korbel, Thorsten Schlomm, Robert G Bristow, Paul C Boutros
Nuclear mutations are well known to drive tumor incidence, aggression and response to therapy. By contrast, the frequency and roles of mutations in the maternally inherited mitochondrial genome are poorly understood. Here we sequence the mitochondrial genomes of 384 localized prostate cancer patients, and identify a median of one mitochondrial single-nucleotide variant (mtSNV) per patient. Some of these mtSNVs occur in recurrent mutational hotspots and associate with aggressive disease. Younger patients have fewer mtSNVs than those who diagnosed at an older age...
September 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28927585/whole-genome-and-transcriptome-sequencing-of-prostate-cancer-identify-new-genetic-alterations-driving-disease-progression
#10
Shancheng Ren, Gong-Hong Wei, Dongbing Liu, Liguo Wang, Yong Hou, Shida Zhu, Lihua Peng, Qin Zhang, Yanbing Cheng, Hong Su, Xiuqing Zhou, Jibin Zhang, Fuqiang Li, Hancheng Zheng, Zhikun Zhao, Changjun Yin, Zengquan He, Xin Gao, Haiyen E Zhau, Chia-Yi Chu, Jason Boyang Wu, Colin Collins, Stanislav V Volik, Robert Bell, Jiaoti Huang, Kui Wu, Danfeng Xu, Dingwei Ye, Yongwei Yu, Lianhui Zhu, Meng Qiao, Hang-Mao Lee, Yuehong Yang, Yasheng Zhu, Xiaolei Shi, Rui Chen, Yang Wang, Weidong Xu, Yanqiong Cheng, Chuanliang Xu, Xu Gao, Tie Zhou, Bo Yang, Jianguo Hou, Li Liu, Zhensheng Zhang, Yao Zhu, Chao Qin, Pengfei Shao, Jun Pang, Leland W K Chung, Jianfeng Xu, Chin-Lee Wu, Weide Zhong, Xun Xu, Yingrui Li, Xiuqing Zhang, Jian Wang, Huanming Yang, Jun Wang, Haojie Huang, Yinghao Sun
BACKGROUND: Global disparities in prostate cancer (PCa) incidence highlight the urgent need to identify genomic abnormalities in prostate tumors in different ethnic populations including Asian men. OBJECTIVE: To systematically explore the genomic complexity and define disease-driven genetic alterations in PCa. DESIGN, SETTING, AND PARTICIPANTS: The study sequenced whole-genome and transcriptome of tumor-benign paired tissues from 65 treatment-naive Chinese PCa patients...
September 15, 2017: European Urology
https://www.readbyqxmd.com/read/28925401/endogenous-androgen-receptor-proteomic-profiling-reveals-genomic-subcomplex-involved-in-prostate-tumorigenesis
#11
S Stelloo, E Nevedomskaya, Y Kim, L Hoekman, O B Bleijerveld, T Mirza, L F A Wessels, W M van Weerden, A F M Altelaar, A M Bergman, W Zwart
Androgen receptor (AR) is a key player in prostate cancer development and progression. Here we applied immunoprecipitation mass spectrometry of endogenous AR in LNCaP cells to identify components of the AR transcriptional complex. In total, 66 known and novel AR interactors were identified in the presence of synthetic androgen, most of which were critical for AR-driven prostate cancer cell proliferation. A subset of AR interactors required for LNCaP proliferation were profiled using chromatin immunoprecipitation assays followed by sequencing, identifying distinct genomic subcomplexes of AR interaction partners...
September 18, 2017: Oncogene
https://www.readbyqxmd.com/read/28912897/genomic-analysis-of-tumor-microenvironment-immune-types-across-14-solid-cancer-types-immunotherapeutic-implications
#12
Yu-Pei Chen, Yu Zhang, Jia-Wei Lv, Ying-Qin Li, Ya-Qin Wang, Qing-Mei He, Xiao-Jing Yang, Ying Sun, Yan-Ping Mao, Jing-Ping Yun, Na Liu, Jun Ma
We performed a comprehensive immuno-genomic analysis of tumor microenvironment immune types (TMITs), which is classified into four groups based on PD-L1+CD8A or PD-L1+cytolytic activity (CYT) expression, across a broad spectrum of solid tumors in order to help identify patients who will benefit from anti- PD-1/PD-L1 therapy. The mRNA sequencing data from The Cancer Genome Atlas (TCGA) of 14 solid cancer types representing 6,685 tumor samples was analyzed. TMIT was classified only for those tumor types that both PD-L1 and CD8A/CYT could prefict mutation and/or neoantigen number...
2017: Theranostics
https://www.readbyqxmd.com/read/28895566/wnt-signalling-in-prostate-cancer
#13
REVIEW
Virginia Murillo-Garzón, Robert Kypta
Genome sequencing and gene expression analyses of prostate tumours have highlighted the potential importance of genetic and epigenetic changes observed in WNT signalling pathway components in prostate tumours - particularly in the development of castration-resistant prostate cancer. WNT signalling is also important in the prostate tumour microenvironment, in which WNT proteins secreted by the tumour stroma promote resistance to therapy, and in prostate cancer stem or progenitor cells, in which WNT-β-catenin signals promote self-renewal or expansion...
September 12, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/28873162/mutation-detection-in-patients-with-advanced-cancer-by-universal-sequencing-of-cancer-related-genes-in-tumor-and-normal-dna-vs-guideline-based-germline-testing
#14
Diana Mandelker, Liying Zhang, Yelena Kemel, Zsofia K Stadler, Vijai Joseph, Ahmet Zehir, Nisha Pradhan, Angela Arnold, Michael F Walsh, Yirong Li, Anoop R Balakrishnan, Aijazuddin Syed, Meera Prasad, Khedoudja Nafa, Maria I Carlo, Karen A Cadoo, Meg Sheehan, Megan H Fleischut, Erin Salo-Mullen, Magan Trottier, Steven M Lipkin, Anne Lincoln, Semanti Mukherjee, Vignesh Ravichandran, Roy Cambria, Jesse Galle, Wassim Abida, Marcia E Arcila, Ryma Benayed, Ronak Shah, Kenneth Yu, Dean F Bajorin, Jonathan A Coleman, Steven D Leach, Maeve A Lowery, Julio Garcia-Aguilar, Philip W Kantoff, Charles L Sawyers, Maura N Dickler, Leonard Saltz, Robert J Motzer, Eileen M O'Reilly, Howard I Scher, Jose Baselga, David S Klimstra, David B Solit, David M Hyman, Michael F Berger, Marc Ladanyi, Mark E Robson, Kenneth Offit
Importance: Guidelines for cancer genetic testing based on family history may miss clinically actionable genetic changes with established implications for cancer screening or prevention. Objective: To determine the proportion and potential clinical implications of inherited variants detected using simultaneous sequencing of the tumor and normal tissue ("tumor-normal sequencing") compared with genetic test results based on current guidelines. Design, Setting, and Participants: From January 2014 until May 2016 at Memorial Sloan Kettering Cancer Center, 10 336 patients consented to tumor DNA sequencing...
September 5, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28842510/impact-of-therapy-on-genomics-and-transcriptomics-in-high-risk-prostate-cancer-treated-with-neoadjuvant-docetaxel-and-androgen-deprivation-therapy
#15
Himisha Beltran, Alexander W Wyatt, Edmund Chedgy, Adam Donoghue, Matti Annala, Evan Warner, Kevin Beja, Michael Sigouros, Fan Mo, Ladan Fazli, Colin C Collins, James A Eastham, Michael J Morris, Mary-Ellen Taplin, Andrea Sboner, Susan Halabi, Martin E Gleave
BACKGROUND: The combination of docetaxel chemotherapy and androgen deprivation therapy (ADT) has become a standard treatment for patients with metastatic prostate cancer. The recently accrued Phase III CALGB 90203 trial was designed to investigate the clinical effectiveness of this treatment approach earlier in the disease. Specimens from this trial offer a unique opportunity to interrogate the acute molecular response to docetaxel and ADT and identify predictive biomarkers. METHODS: We evaluated baseline clinical data, needle biopsies and radical prostatectomy (RP) specimens from 52 (of 788) patients enrolled on CALGB 90203 at one high volume center...
August 25, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28819847/negative-enrichment-and-isolation-of-circulating-tumor-cells-for-whole-genome-amplification
#16
Nisha Kanwar, Susan J Done
Circulating tumor cells (CTCs) are a rare population of cells found in the peripheral blood of patients with many types of cancer such as breast, prostate, colon, and lung cancers. Higher numbers of these cells in blood are associated with a poorer prognosis of patients. Genomic profiling of CTCs would help characterize markers specific for the identification of these cells in blood, and also define genomic alterations that give these cells a metastatic advantage over other cells in the primary tumor. Here, we describe an immunomagnetic method to enrich CTCs from the blood of patients with breast cancer, followed by single-cell laser capture microdissection to isolate single CTCs...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28814964/milk-disrupts-p53-and-dnmt1-the-guardians-of-the-genome-implications-for-acne-vulgaris-and-prostate-cancer
#17
Bodo C Melnik
There is accumulating evidence that milk shapes the postnatal metabolic environment of the newborn infant. Based on translational research, this perspective article provides a novel mechanistic link between milk intake and milk miRNA-regulated gene expression of the transcription factor p53 and DNA methyltransferase 1 (DNMT1), two guardians of the human genome, that control transcriptional activity, cell survival, and apoptosis. Major miRNAs of milk, especially miRNA-125b, directly target TP53 and complex p53-dependent gene regulatory networks...
2017: Nutrition & Metabolism
https://www.readbyqxmd.com/read/28811844/lsd1-dual-function-in-mediating-epigenetic-corruption-of-the-vitamin-d-signaling-in-prostate-cancer
#18
Sebastiano Battaglia, Ellen Karasik, Bryan Gillard, Jennifer Williams, Trisha Winchester, Michael T Moser, Dominic J Smiraglia, Barbara A Foster
BACKGROUND: Lysine-specific demethylase 1A (LSD1) is a key regulator of the androgen (AR) and estrogen receptors (ER), and LSD1 levels correlate with tumor aggressiveness. Here, we demonstrate that LSD1 regulates vitamin D receptor (VDR) activity and is a mediator of 1,25(OH)2-D3 (vitamin D) action in prostate cancer (PCa). METHODS: Athymic nude mice were xenografted with CWR22 cells and monitored weekly after testosterone pellet removal. Expression of LSD1 and VDR (IHC) were correlated with tumor growth using log-rank test...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28811834/high-risk-human-papilloma-viruses-hpvs-are-present-in-benign-prostate-tissues-before-development-of-hpv-associated-prostate-cancer
#19
Wendy K Glenn, Christopher C Ngan, Timothy G Amos, Richard J Edwards, Joshua Swift, Louise Lutze-Mann, Fei Shang, Noel J Whitaker, James S Lawson
BACKGROUND: Although high risk HPVs are associated with an increased risk of prostate cancer it is not known if they have a causal role. The purpose of this study is to investigate the potential role of human papilloma viruses (HPVs) in prostate cancer. The aims are (i) to investigate the presence and confirm the identity of high risk HPVs in benign prostate tissues prior to the development of HPV positive prostate cancer in the same patients, and (ii) to determine if HPVs are biologically active...
2017: Infectious Agents and Cancer
https://www.readbyqxmd.com/read/28802562/current-research-development-of-single-cell-genome-in-urological-tumor
#20
Ziyi Cao, Song Wu
The technique of whole genome amplification is advancing rapidly and generating attention on detecting genomic lesions in individual cancer cells. Also, single-cell genome could label the uniqueness of each cell, its individual mutations and structural variations especially in cancer studies. In this Review, we provide the insight into the current state of single-cell genome in urological tumor mainly including kidney cancer, bladder cancer and prostate cancer. We put more forward on the new progress of the technique used by single-cell genomes and different results of the genes transform on random tumor tissue from single cell isolated on account of tumor heterogeneity...
August 9, 2017: International Journal of Biochemistry & Cell Biology
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