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prostate cancer genomic sequencing

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https://www.readbyqxmd.com/read/29690565/prostate-cancer-genomics-recent-advances-and-the-prevailing-underrepresentation-from-racial-and-ethnic-minorities
#1
REVIEW
Shyh-Han Tan, Gyorgy Petrovics, Shiv Srivastava
Prostate cancer (CaP) is the most commonly diagnosed non-cutaneous cancer and the second leading cause of male cancer deaths in the United States. Among African American (AA) men, CaP is the most prevalent malignancy, with disproportionately higher incidence and mortality rates. Even after discounting the influence of socioeconomic factors, the effect of molecular and genetic factors on racial disparity of CaP is evident. Earlier studies on the molecular basis for CaP disparity have focused on the influence of heritable mutations and single-nucleotide polymorphisms (SNPs)...
April 22, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29673712/update-on-systemic-prostate-cancer-therapies-management-of-metastatic-castration-resistant-prostate-cancer-in-the-era-of-precision-oncology
#2
REVIEW
Philipp Nuhn, Johann S De Bono, Karim Fizazi, Stephen J Freedland, Maurizio Grilli, Philip W Kantoff, Guru Sonpavde, Cora N Sternberg, Srinivasan Yegnasubramanian, Emmanuel S Antonarakis
CONTEXT: Introduction of novel agents for the management of advanced prostate cancer provides a range of treatment options with notable benefits for men with metastatic castration-resistant prostate cancer (mCRPC). At the same time, understanding of optimal patient selection, effective sequential use, and development of resistance patterns remains incomplete. OBJECTIVE: To review current systemic therapies and recent advances in drug development for mCRPC and strategies to aid in patient selection and optimal sequencing...
April 16, 2018: European Urology
https://www.readbyqxmd.com/read/29673323/indel-detection-from-dna-and-rna-sequencing-data-with-transindel
#3
Rendong Yang, Jamie L Van Etten, Scott M Dehm
BACKGROUND: Insertions and deletions (indels) are a major class of genomic variation associated with human disease. Indels are primarily detected from DNA sequencing (DNA-seq) data but their transcriptional consequences remain unexplored due to challenges in discriminating medium-sized and large indels from splicing events in RNA-seq data. RESULTS: Here, we developed transIndel, a splice-aware algorithm that parses the chimeric alignments predicted by a short read aligner and reconstructs the mid-sized insertions and large deletions based on the linear alignments of split reads from DNA-seq or RNA-seq data...
April 19, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29666160/most-human-introns-are-recognized-via-multiple-and-tissue-specific-branchpoints
#4
Jose Mario Bello Pineda, Robert K Bradley
Although branchpoint recognition is an essential component of intron excision during the RNA splicing process, the branchpoint itself is frequently assumed to be a basal, rather than regulatory, sequence feature. However, this assumption has not been systematically tested due to the technical difficulty of identifying branchpoints and quantifying their usage. Here, we analyzed ∼1.31 trillion reads from 17,164 RNA sequencing data sets to demonstrate that almost all human introns contain multiple branchpoints...
April 17, 2018: Genes & Development
https://www.readbyqxmd.com/read/29662167/sequencing-of-prostate-cancers-identifies-new-cancer-genes-routes-of-progression-and-drug-targets
#5
David C Wedge, Gunes Gundem, Thomas Mitchell, Dan J Woodcock, Inigo Martincorena, Mohammed Ghori, Jorge Zamora, Adam Butler, Hayley Whitaker, Zsofia Kote-Jarai, Ludmil B Alexandrov, Peter Van Loo, Charlie E Massie, Stefan Dentro, Anne Y Warren, Clare Verrill, Dan M Berney, Nening Dennis, Sue Merson, Steve Hawkins, William Howat, Yong-Jie Lu, Adam Lambert, Jonathan Kay, Barbara Kremeyer, Katalin Karaszi, Hayley Luxton, Niedzica Camacho, Luke Marsden, Sandra Edwards, Lucy Matthews, Valeria Bo, Daniel Leongamornlert, Stuart McLaren, Anthony Ng, Yongwei Yu, Hongwei Zhang, Tokhir Dadaev, Sarah Thomas, Douglas F Easton, Mahbubl Ahmed, Elizabeth Bancroft, Cyril Fisher, Naomi Livni, David Nicol, Simon Tavaré, Pelvender Gill, Christopher Greenman, Vincent Khoo, Nicholas Van As, Pardeep Kumar, Christopher Ogden, Declan Cahill, Alan Thompson, Erik Mayer, Edward Rowe, Tim Dudderidge, Vincent Gnanapragasam, Nimish C Shah, Keiran Raine, David Jones, Andrew Menzies, Lucy Stebbings, Jon Teague, Steven Hazell, Cathy Corbishley, Johann de Bono, Gerhardt Attard, William Isaacs, Tapio Visakorpi, Michael Fraser, Paul C Boutros, Robert G Bristow, Paul Workman, Chris Sander, Freddie C Hamdy, Andrew Futreal, Ultan McDermott, Bissan Al-Lazikani, Andrew G Lynch, G Steven Bova, Christopher S Foster, Daniel S Brewer, David E Neal, Colin S Cooper, Rosalind A Eeles
Prostate cancer represents a substantial clinical challenge because it is difficult to predict outcome and advanced disease is often fatal. We sequenced the whole genomes of 112 primary and metastatic prostate cancer samples. From joint analysis of these cancers with those from previous studies (930 cancers in total), we found evidence for 22 previously unidentified putative driver genes harboring coding mutations, as well as evidence for NEAT1 and FOXA1 acting as drivers through noncoding mutations. Through the temporal dissection of aberrations, we identified driver mutations specifically associated with steps in the progression of prostate cancer, establishing, for example, loss of CHD1 and BRCA2 as early events in cancer development of ETS fusion-negative cancers...
April 16, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29661807/genetically-engineered-mouse-models-of-prostate-cancer-in-the-postgenomic-era
#6
Juan M Arriaga, Cory Abate-Shen
Recent genomic sequencing analyses have unveiled the spectrum of genomic alterations that occur in primary and advanced prostate cancer, raising the question of whether the corresponding genes are functionally relevant for prostate tumorigenesis, and whether such functions are associated with particular disease stages. In this review, we describe genetically engineered mouse models (GEMMs) of prostate cancer, focusing on those that model genomic alterations known to occur in human prostate cancer. We consider whether the phenotypes of GEMMs based on gain or loss of function of the relevant genes provide reliable counterparts to study the predicted consequences of the corresponding genomic alterations as occur in human prostate cancer, and we discuss exceptions in which the GEMMs do not fully emulate the expected phenotypes...
April 16, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/29658782/phylogenetic-copy-number-factorization-of-multiple-tumor-samples
#7
Simone Zaccaria, Mohammed El-Kebir, Gunnar W Klau, Benjamin J Raphael
Cancer is an evolutionary process driven by somatic mutations. This process can be represented as a phylogenetic tree. Constructing such a phylogenetic tree from genome sequencing data is a challenging task due to the many types of mutations in cancer and the fact that nearly all cancer sequencing is of a bulk tumor, measuring a superposition of somatic mutations present in different cells. We study the problem of reconstructing tumor phylogenies from copy-number aberrations (CNAs) measured in bulk-sequencing data...
April 16, 2018: Journal of Computational Biology: a Journal of Computational Molecular Cell Biology
https://www.readbyqxmd.com/read/29650553/enduring-epigenetic-landmarks-define-the-cancer-microenvironment
#8
Ruth Pidsley, Mitchell G Lawrence, Elena Zotenko, Birunthi Niranjan, Aaron Statham, Jenny Song, Roman M Chabanon, Wenjia Qu, Hong Wang, Michelle Richards, Shalima S Nair, Nicola J Armstrong, Hieu T Nim, Melissa Papargiris, Preetika Balanathan, Hugh French, Timothy Peters, Sam Norden, Andrew Ryan, John Pedersen, James Kench, Roger J Daly, Lisa G Horvath, Phillip Stricker, Mark Frydenberg, Renea A Taylor, Clare Stirzaker, Gail P Risbridger, Susan J Clark
The growth and progression of solid tumors involves dynamic cross-talk between cancer epithelium and the surrounding microenvironment. To date, molecular profiling has largely been restricted to the epithelial component of tumors; therefore, features underpinning the persistent protumorigenic phenotype of the tumor microenvironment are unknown. Using whole-genome bisulfite sequencing, we show for the first time that cancer-associated fibroblasts (CAFs) from localized prostate cancer display remarkably distinct and enduring genome-wide changes in DNA methylation, significantly at enhancers and promoters, compared to nonmalignant prostate fibroblasts (NPFs)...
April 12, 2018: Genome Research
https://www.readbyqxmd.com/read/29643985/replication-incompetent-gammaretroviral-and-lentiviral-vector-based-insertional-mutagenesis-screens-identify-prostate-cancer-progression-genes
#9
Victor M Bii, Casey P Collins, Jonah D Hocum, Grant D Trobridge
Replication-incompetent gammaretroviral (γRV) and lentiviral (LV) vectors have both been used in insertional mutagenesis screens to identify cancer drivers. In this approach the vectors stably integrate in the host cell genome and induce cancers by dysregulating nearby genes. The cells that contain a retroviral vector provirus in or near a proto-oncogene or tumor suppressor are preferentially enriched in a tumor. γRV and LV vectors have different integration profiles and genotoxic potential, making them potentially complementary tools for insertional mutagenesis screens...
March 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29616087/identification-of-potential-key-genes-and-high-frequency-mutant-genes-in-prostate-cancer-by-using-rna-seq-data
#10
Ze Zhang, He Wu, Hong Zhou, Yunhe Gu, Yufeng Bai, Shiliang Yu, Ruihua An, Jiping Qi
The aim of the present study was to identify potential key genes and single nucleotide variations (SNVs) in prostate cancer. RNA sequencing (RNA-seq) data, GSE22260, were downloaded from the Gene Expression Omnibus database, including 4 prostate cancer samples and 4 normal tissues samples. RNA-Seq reads were processed using Tophat and differentially-expressed genes (DEGs) were identified using the Cufflinks package. Gene Ontology enrichment analysis of DEGs was performed. Subsequently, Seqpos was used to identify the potential upstream regulatory elements of DEGs...
April 2018: Oncology Letters
https://www.readbyqxmd.com/read/29610475/the-long-tail-of-oncogenic-drivers-in-prostate-cancer
#11
Joshua Armenia, Stephanie A M Wankowicz, David Liu, Jianjiong Gao, Ritika Kundra, Ed Reznik, Walid K Chatila, Debyani Chakravarty, G Celine Han, Ilsa Coleman, Bruce Montgomery, Colin Pritchard, Colm Morrissey, Christopher E Barbieri, Himisha Beltran, Andrea Sboner, Zafeiris Zafeiriou, Susana Miranda, Craig M Bielski, Alexander V Penson, Charlotte Tolonen, Franklin W Huang, Dan Robinson, Yi Mi Wu, Robert Lonigro, Levi A Garraway, Francesca Demichelis, Philip W Kantoff, Mary-Ellen Taplin, Wassim Abida, Barry S Taylor, Howard I Scher, Peter S Nelson, Johann S de Bono, Mark A Rubin, Charles L Sawyers, Arul M Chinnaiyan, Nikolaus Schultz, Eliezer M Van Allen
Comprehensive genomic characterization of prostate cancer has identified recurrent alterations in genes involved in androgen signaling, DNA repair, and PI3K signaling, among others. However, larger and uniform genomic analysis may identify additional recurrently mutated genes at lower frequencies. Here we aggregate and uniformly analyze exome sequencing data from 1,013 prostate cancers. We identify and validate a new class of E26 transformation-specific (ETS)-fusion-negative tumors defined by mutations in epigenetic regulators, as well as alterations in pathways not previously implicated in prostate cancer, such as the spliceosome pathway...
April 2, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29574703/genomic-alterations-in-plasma-dna-from-patients-with-metastasized-prostate-cancer-receiving-abiraterone-or-enzalutamide
#12
Jelena Belic, Ricarda Graf, Thomas Bauernhofer, Yauheniya Cherkas, Peter Ulz, Julie Waldispuehl-Geigl, Samantha Perakis, Michael Gormley, Jaymala Patel, Weimin Li, Jochen B Geigl, Denis Smirnov, Ellen Heitzer, Mitchell Gross, Michael R Speicher
In patients with metastatic castrate resistant prostate cancer (mCRPC), circulating tumor DNA (ctDNA) analysis offers novel opportunities for the development of non-invasive biomarkers informative of treatment response with novel agents targeting the androgen-receptor (AR) pathway, such as abiraterone or enzalutamide. However, the relationship between ctDNA abundance, detectable somatic genomic alterations and clinical progression of mCRPC remains unexplored. Our study aimed to investigate changes in plasma DNA during disease progression and their associations with clinical variables in mCRPC patients...
March 25, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29574604/evolution-of-melanoma-antigen-a11-magea11-during-primate-phylogeny
#13
Christopher S Willett, Elizabeth M Wilson
Melanoma antigen-A11 (MAGE-A11) is an X-linked and primate-specific steroid hormone receptor transcriptional coregulator and proto-oncogenic protein whose increased expression promotes the growth of prostate cancer. The MAGEA11 gene is expressed at low levels in normal human testis, ovary, and endometrium, and at highest levels in castration-resistant prostate cancer. Annotated genome predictions throughout the surviving primate lineage show that MAGEA11 acquired three 5' coding exons unique within the MAGEA subfamily during the evolution of New World monkeys (NWM), Old World monkeys (OWM), and apes...
March 24, 2018: Journal of Molecular Evolution
https://www.readbyqxmd.com/read/29553949/recent-advances-in-the-management-of-metastatic-prostate-cancer-optimizing-use-of-existing-therapies-while-searching-for-novel-interventions
#14
Theodore Gourdin
PURPOSE OF REVIEW: Summarizes recent advances in the treatment of metastatic castration-sensitive and castration-resistant prostate cancer. RECENT FINDINGS: New randomized data suggest a survival advantage to early abiraterone in castration-sensitive metastatic prostate cancer. Prospective and retrospective studies are examining sequencing of existing cytotoxic and androgen-receptor-targeted therapies in both castration-sensitive and castration-resistant disease...
May 2018: Current Opinion in Oncology
https://www.readbyqxmd.com/read/29494651/a-streamlined-workflow-for-single-cells-genome-wide-copy-number-profiling-by-low-pass-sequencing-of-lm-pcr-whole-genome-amplification-products
#15
Alberto Ferrarini, Claudio Forcato, Genny Buson, Paola Tononi, Valentina Del Monaco, Mario Terracciano, Chiara Bolognesi, Francesca Fontana, Gianni Medoro, Rui Neves, Birte Möhlendick, Karim Rihawi, Andrea Ardizzoni, Semini Sumanasuriya, Penny Flohr, Maryou Lambros, Johann de Bono, Nikolas H Stoecklein, Nicolò Manaresi
Chromosomal instability and associated chromosomal aberrations are hallmarks of cancer and play a critical role in disease progression and development of resistance to drugs. Single-cell genome analysis has gained interest in latest years as a source of biomarkers for targeted-therapy selection and drug resistance, and several methods have been developed to amplify the genomic DNA and to produce libraries suitable for Whole Genome Sequencing (WGS). However, most protocols require several enzymatic and cleanup steps, thus increasing the complexity and length of protocols, while robustness and speed are key factors for clinical applications...
2018: PloS One
https://www.readbyqxmd.com/read/29465803/olaparib-is-effective-in-combination-with-and-as-maintenance-therapy-after-first-line-endocrine-therapy-in-prostate-cancer-cells
#16
Gertrud E Feiersinger, Kristina Trattnig, Peter D Leitner, Fabian Guggenberger, Alexander Oberhuber, Sarah Peer, Martin Hermann, Ira Skvortsova, Jana Vrbkova, Jan Bouchal, Zoran Culig, Frédéric R Santer
A number of prostate cancer (PCa)-specific genomic aberrations (denominated BRCAness genes) have been discovered implicating sensitivity to PARP inhibition within the concept of synthetic lethality. Recent clinical studies show favorable results for the PARP inhibitor Olaparib used as single agent for treatment of metastatic castration-resistant PCa. Using 2D and 3D cell culture models mimicking the different treatment and progression stages of PCa we evaluated a potential use for Olaparib in combination with first-line endocrine treatments, androgen deprivation and complete androgen blockade, and as a maintenance therapy following on from endocrine therapy...
February 21, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29463374/nano-vesicles-are-a-potential-tool-to-monitor-therapeutic-efficacy-of-carbon-ion-radiotherapy-in-prostate-cancer
#17
Qi Yu, Ping Li, Meilin Weng, Shuang Wu, Yafang Zhang, Xue Chen, Qing Zhang, Guangxia Shen, Xianting Ding, Shen Fu
Exosomes are nano-vesicles that contribute to the effectiveness of many treatments. The aim of this study was to identify profiles of microRNA (miRNA) contained in serum exosomes that are differentially regulated in patients with prostate cancer undergoing carbon ion radiotherapy (CIRT). RNA was extracted from serum exosomes of eight patients with localized prostate cancer before and after CIRT, and miRNA was analyzed by the next generation sequencing. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the major signaling pathways associated with the proliferation of prostate cancer cells, such as MAPK, PI3K-AKT, mTOR, and AMPK may be implicated in the mechanism of CIRT action...
January 1, 2018: Journal of Biomedical Nanotechnology
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
#18
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
#19
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
#20
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
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