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prostate cancer genomic sequencing

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https://www.readbyqxmd.com/read/27907910/a-mononucleotide-repeat-in-prrt2-is-an-important-frequent-target-of-mismatch-repair-deficiency-in-cancer
#1
Inês Teles Alves, David Cano, René Böttcher, Hetty van der Korput, Winand Dinjens, Guido Jenster, Jan Trapman
The DNA mismatch repair (MMR) system corrects DNA replication mismatches thereby contributing to the maintenance of genomic stability. MMR deficiency has been observed in prostate cancer but its impact on the genomic landscape of these tumours is not known. In order to identify MMR associated mutations in prostate cancer we have performed whole genome sequencing of the MMR deficient PC346C prostate cancer cell line. We detected a total of 1196 mutations in PC346C which was 1.5-fold higher compared to a MMR proficient prostate cancer sample (G089)...
November 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27900359/homozygous-inactivation-of-chek2-is-linked-to-a-familial-case-of-multiple-primary-lung-cancer-with-accompanying-cancers-in-other-organs
#2
Yoji Kukita, Jiro Okami, Noriko Yoneda-Kato, Ikuko Nakamae, Takeshi Kawabata, Masahiko Higashiyama, Junya Kato, Ken Kodama, Kikuya Kato
In clinical practice, there are a number of cancer patients with clear family histories, but the patients lack mutations in known familial cancer syndrome genes. Recent advances in genomic technologies have enhanced the possibility of identifying causative genes in such cases. Two siblings, an elder sister and a younger brother, were found to have multiple primary lung cancers at the age of 60. The former subsequently developed breast cancer and had a history of uterine myoma. The latter had initially developed prostate cancer at the age of 59 and had a history of colon cancer...
November 2016: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/27899188/familial-prostate-cancer
#3
Veda N Giri, Jennifer L Beebe-Dimmer
Prostate cancer is the most commonly diagnosed cancer among men in the United States as well as most Western countries. A significant proportion of men report having a positive family history of prostate cancer in a first-degree relative (father, brother, son), which is important in that family history is one of the only established risk factors for the disease and plays a role in decision-making for prostate cancer screening. Familial aggregation of prostate cancer is considered a surrogate marker of genetic susceptibility to developing the disease, but shared environment cannot be excluded as an explanation for clustering of cases among family members...
October 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/27867534/nanog-reprograms-prostate-cancer-cells-to-castration-resistance-via-dynamically-repressing-and-engaging-the-ar-foxa1-signaling-axis
#4
Collene R Jeter, Bigang Liu, Yue Lu, Hsueh-Ping Chao, Dingxiao Zhang, Xin Liu, Xin Chen, Qiuhui Li, Kiera Rycaj, Tammy Calhoun-Davis, Li Yan, Qiang Hu, Jianmin Wang, Jianjun Shen, Song Liu, Dean G Tang
The pluripotency transcription factor NANOG has been implicated in tumor development, and NANOG-expressing cancer cells manifest stem cell properties that sustain tumor homeostasis, mediate therapy resistance and fuel tumor progression. However, how NANOG converges on somatic circuitry to trigger oncogenic reprogramming remains obscure. We previously reported that inducible NANOG expression propels the emergence of aggressive castration-resistant prostate cancer phenotypes. Here we first show that endogenous NANOG is required for the growth of castration-resistant prostate cancer xenografts...
2016: Cell Discovery
https://www.readbyqxmd.com/read/27851748/chromosomal-instability-estimation-based-on-next-generation-sequencing-and-single-cell-genome-wide-copy-number-variation-analysis
#5
Stephanie B Greene, Angel E Dago, Laura J Leitz, Yipeng Wang, Jerry Lee, Shannon L Werner, Steven Gendreau, Premal Patel, Shidong Jia, Liangxuan Zhang, Eric K Tucker, Michael Malchiodi, Ryon P Graf, Ryan Dittamore, Dena Marrinucci, Mark Landers
Genomic instability is a hallmark of cancer often associated with poor patient outcome and resistance to targeted therapy. Assessment of genomic instability in bulk tumor or biopsy can be complicated due to sample availability, surrounding tissue contamination, or tumor heterogeneity. The Epic Sciences circulating tumor cell (CTC) platform utilizes a non-enrichment based approach for the detection and characterization of rare tumor cells in clinical blood samples. Genomic profiling of individual CTCs could provide a portrait of cancer heterogeneity, identify clonal and sub-clonal drivers, and monitor disease progression...
2016: PloS One
https://www.readbyqxmd.com/read/27819678/tet2-binds-the-androgen-receptor-and-loss-is-associated-with-prostate-cancer
#6
M L Nickerson, S Das, K M Im, S Turan, S I Berndt, H Li, H Lou, S A Brodie, J N Billaud, T Zhang, A J Bouk, D Butcher, Z Wang, L Sun, K Misner, W Tan, A Esnakula, D Esposito, W Y Huang, R N Hoover, M A Tucker, J R Keller, J Boland, K Brown, S K Anderson, L E Moore, W B Isaacs, S J Chanock, M Yeager, M Dean, T Andresson
Genetic alterations associated with prostate cancer (PCa) may be identified by sequencing metastatic tumour genomes to identify molecular markers at this lethal stage of disease. Previously, we characterized somatic alterations in metastatic tumours in the methylcytosine dioxygenase ten-eleven translocation 2 (TET2), which is altered in 5-15% of myeloid, kidney, colon and PCas. Genome-wide association studies previously identified non-coding risk variants associated with PCa and melanoma. We perform fine-mapping of PCa risk across TET2 using genotypes from the PEGASUS case-control cohort and identify six new risk variants in introns 1 and 2...
November 7, 2016: Oncogene
https://www.readbyqxmd.com/read/27818231/epigenetic-reactivation-of-rassf1a-by-phenethyl-isothiocyanate-peitc-and-promotion-of-apoptosis-in-lncap-cells
#7
Sarandeep S S Boyanapalli, Wenji Li, Francisco Fuentes, Yue Guo, Christina N Ramirez, Ximena-Parades Gonzalez, Douglas Pung, Ah-Ng Tony Kong
Epigenetic silencing of tumor suppressor genes is a phenomenon frequently observed in multiple cancers. Ras-association domain family 1 isoform A (RASSF1A) is a well-characterized tumor suppressor that belongs to the Ras-association domain family. Several studies have demonstrated that hypermethylation of the RASSF1A promoter is frequently observed in lung, prostate, and breast cancers. Phenethyl isothiocyanate (PEITC), a phytochemical abundant in cruciferous vegetables, possesses chemopreventive activities; however, its potential involvement in epigenetic mechanisms remains elusive...
November 3, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27813113/promoter-cpg-site-methylation-of-the-kai1-metastasis-suppressor-gene-contributes-to-its-epigenetic-repression-in-prostate-cancer
#8
Jaeseob Lee, Moon-Sung Lee, Doo-Il Jeoung, Young-Myeong Kim, Hansoo Lee
BACKGROUND: Repression of the KAI1 metastasis suppressor gene is closely associated with malignancy and poor prognosis in many human cancer types including prostate cancer. Since gene repression in human cancers frequently results from epigenetic alterations by DNA methylation and histone modifications, we examined whether the KAI1 gene becomes silenced through these epigenetic mechanisms in prostate cancer. METHODS: KAI1 mRNA and protein levels were determined by RT-PCR and immunoblotting analyses, respectively...
November 3, 2016: Prostate
https://www.readbyqxmd.com/read/27807836/computational-methods-and-correlation-of-exon-skipping-events-with-splicing-transcription-and-epigenetic-factors
#9
Jianbo Wang, Zhenqing Ye, Tim H Huang, Huidong Shi, Victor X Jin
Alternative splicing is widely recognized for playing roles in regulating genes and creating gene diversity. Consequently the identification and quantification of differentially spliced transcripts are pivotal for transcriptome analysis. However, how these diversified isoforms are spliced during genomic transcription and protein expression and what biological factors might influence the regulation of this are still required for further exploration. The advances in next-generation sequencing of messenger RNA (RNA-seq) have enabled us to survey gene expression and splicing more accurately...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27800606/promoting-cancer-control-in-africa-with-ubuntu-a-report-of-the-african-organization-for-research-and-training-in-africa-aortic-10-th-conference-2015-in-marrakech-morocco
#10
Kenneth O Simbiri, Christopher K Williams, Marcella Macaluso, Antonio Giordano
The objectives of the African Organization for Research and Training in Cancer (AORTIC), includes bringing products of decades of advances in cancer research to African populations through local and international collaboration. The consistent and huge growth in participation in the conferences and the diversity of the nations is a witness to the success of the organization thus far. The theme for the Tenth AORTIC International Conference on Cancer in Africa in Morocco in 2015 was "Road map to Cancer Control in Africa" and topics of discussion of paramount importance for low- and middle-income African countries included childhood cancers such as BL, cancers of the cervix, breast, and prostate; cancers associated with HIV-infection such as cervical, vulvar, and anal; as well as cancer care challenges associated with palliative care...
November 1, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27785154/whole-genome-sequencing-uncovers-a-novel-ind-16-metallo-%C3%AE-lactamase-from-an-extensively-drug-resistant-chryseobacterium-indologenes-strain-j31
#11
Tingting Wang, Xiawei Jiang, Chunyan Feng, Ang Li, Huihui Dong, Shaoqiang Wu, Beiwen Zheng
BACKGROUND: Chryseobacterium indologenes is an emerging opportunistic pathogen in hospital-acquired infection, which is intrinsically resistant to most antimicrobial agents against gram-negative bacteria. In the purpose of extending our understanding of the resistance mechanism of C. indologenes, we sequenced and analyzed the genome of an extensively antibiotic resistant C. indologenes strain, isolated from a Chinese prostate cancer patient. We also investigated the presence of antibiotic resistance genes, particularly metallo-β-lactamase (MBL) genes, and performed a comparative genomic analysis with other Chryseobacterium species...
2016: Gut Pathogens
https://www.readbyqxmd.com/read/27756888/mismatch-repair-deficiency-may-be-common-in-ductal-adenocarcinoma-of-the-prostate
#12
Michael T Schweizer, Heather H Cheng, Maria S Tretiakova, Funda Vakar-Lopez, Nola Klemfuss, Eric Q Konnick, Elahe A Mostaghel, Peter S Nelson, Evan Y Yu, Bruce Montgomery, Lawrence D True, Colin C Pritchard
Precision oncology entails making treatment decisions based on a tumor's molecular characteristics. For prostate cancer, identifying clinically relevant molecular subgroups is challenging, as molecular profiling is not routine outside of academic centers. Since histologic variants of other cancers correlates with specific genomic alterations, we sought to determine if ductal adenocarcinoma of the prostate (dPC) - a rare and aggressive histopathologic variant - was associated with any recurrent actionable mutations...
October 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27753448/the-molecular-underpinnings-of-prostate-cancer-impacts-on-management-and-pathology-practice
#13
REVIEW
Daniel Nava Rodrigues, Gunther Boysen, Semini Sumanasuriya, George Seed, Angelo M De Marzo, Johann de Bono
Prostate cancer (PCa) is a clinically heterogeneous disease and current treatment strategies are based largely on anatomical and pathological parameters. In the recent past, several DNA sequencing studies of primary and advanced PCa have revealed recurrent patterns of genomic aberrations that expose mechanisms of resistance to available therapies and potential new drug targets. Suppression of androgen receptor (AR) signalling is the cornerstone of advanced prostate cancer treatment. Genomic aberrations of the androgen receptor or alternative splicing of its mRNA are increasingly recognised as biomarkers of resistance to AR-targeted therapies such as abiraterone or enzalutamide...
October 18, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27749331/the-role-of-next-generation-sequencing-in-castration-resistant-prostate-cancer-treatment
#14
Daniel H Hovelson, Scott A Tomlins
Molecular biomarkers play little role in the current treatment of metastatic castration-resistant prostate cancer (CRPC). The advent of next-generation sequencing (NGS) has enabled the comprehensive molecular characterization of the genomic and transcriptomic landscape of both untreated primary prostate cancer and CRPC. Recent studies demonstrating the feasibility of interinstitution studies obtaining and NGS profiling of metastatic biopsies, targeted NGS approaches applicable to routine formalin-fixed, paraffin-embedded specimens, and NGS approaches applicable to circulating DNA and circulating tumor cells portend near-term adoption of NGS approaches in the management and treatment of CRPC...
September 2016: Cancer Journal
https://www.readbyqxmd.com/read/27738762/molecular-pathological-epidemiology-new-developing-frontiers-of-big-data-science-to-study-etiologies-and-pathogenesis
#15
Tsuyoshi Hamada, NaNa Keum, Reiko Nishihara, Shuji Ogino
Molecular pathological epidemiology (MPE) is an integrative field that utilizes molecular pathology to incorporate interpersonal heterogeneity of a disease process into epidemiology. In each individual, the development and progression of a disease are determined by a unique combination of exogenous and endogenous factors, resulting in different molecular and pathological subtypes of the disease. Based on "the unique disease principle," the primary aim of MPE is to uncover an interactive relationship between a specific environmental exposure and disease subtypes in determining disease incidence and mortality...
October 13, 2016: Journal of Gastroenterology
https://www.readbyqxmd.com/read/27705925/mutational-load-of-the-mitochondrial-genome-predicts-pathological-features-and-biochemical-recurrence-in-prostate-cancer
#16
Anton M F Kalsbeek, Eva F K Chan, Judith Grogan, Desiree C Petersen, Weerachai Jaratlerdsiri, Ruta Gupta, Ruth J Lyons, Anne-Maree Haynes, Lisa G Horvath, James G Kench, Phillip D Stricker, Vanessa M Hayes
Prostate cancer management is complicated by extreme disease heterogeneity, which is further limited by availability of prognostic biomarkers. Recognition of prostate cancer as a genetic disease has prompted a focus on the nuclear genome for biomarker discovery, with little attention given to the mitochondrial genome. While it is evident that mitochondrial DNA (mtDNA) mutations are acquired during prostate tumorigenesis, no study has evaluated the prognostic value of mtDNA variation. Here we used next-generation sequencing to interrogate the mitochondrial genomes from prostate tissue biopsies and matched blood of 115 men having undergone a radical prostatectomy for which there was a mean of 107 months clinical follow-up...
October 5, 2016: Aging
https://www.readbyqxmd.com/read/27688072/treatment-of-prostate-cancer-cells-with-s-adenosylmethionine-leads-to-genome-wide-alterations-in-transcription-profiles
#17
Thomas Schmidt, Andreas Leha, Gabriela Salinas-Riester
The hypomethylation of DNA may support tumor progression; however, the mechanism underlying this relationship is not clear. Several studies have demonstrated that the in vitro application of the methyl donor S-adenosylmethionine (SAM) leads to promoter remethylation and the downregulation of proto-oncogene expression in cancer cells. It is not clear if this represents a general mechanism of SAM or is limited to selected genes. We examined this problem using new bisulfite sequencing and transcriptomic technologies...
September 26, 2016: Gene
https://www.readbyqxmd.com/read/27672034/crosstalk-between-androgen-and-pro-inflammatory-signaling-remodels-androgen-receptor-and-nf-%C3%AE%C2%BAb-cistrome-to-reprogram-the-prostate-cancer-cell-transcriptome
#18
Marjo Malinen, Einari A Niskanen, Minna U Kaikkonen, Jorma J Palvimo
Inflammatory processes and androgen signaling are critical for the growth of prostate cancer (PC), the most common cancer among males in Western countries. To understand the importance of potential interplay between pro-inflammatory and androgen signaling for gene regulation, we have interrogated the crosstalk between androgen receptor (AR) and NF-κB, a key transcriptional mediator of inflammatory responses, by utilizing genome-wide chromatin immunoprecipitation sequencing and global run-on sequencing in PC cells...
September 26, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27645052/new-roles-for-nuclear-receptors-in-prostate-cancer
#19
Damien A Leach, Suzanne M Powell, Charlotte Bevan
Prostate cancer has, for decades, been treated by inhibiting androgen signalling. This is effective in the majority of patients, but inevitably resistance develops and patients progress to life-threatening metastatic disease - hence the quest for new effective therapies for "castrate-resistant" prostate cancer (CRPC). Studies into what pathways can drive tumour recurrence under these conditions has identified several other nuclear receptor signalling pathways as potential drivers or modulators of CRPC. The nuclear receptors constitute a large (48 members) superfamily of transcription factors sharing a common modular functional structure...
September 19, 2016: Endocrine-related Cancer
https://www.readbyqxmd.com/read/27641228/global-analysis-of-transcription-in-castration-resistant-prostate-cancer-cells-uncovers-active-enhancers-and-direct-androgen-receptor-targets
#20
Sari Toropainen, Einari A Niskanen, Marjo Malinen, Päivi Sutinen, Minna U Kaikkonen, Jorma J Palvimo
Androgen receptor (AR) is a male sex steroid-activated transcription factor (TF) that plays a critical role in prostate cancers, including castration-resistant prostate cancers (CRPC) that typically express amplified levels of the AR. CRPC-derived VCaP cells display an excessive number of chromatin AR-binding sites (ARBs) most of which localize to distal inter- or intragenic regions. Here, we analyzed direct transcription programs of the AR in VCaP cells using global nuclear run-on sequencing (GRO-seq) and integrated the GRO-seq data with the ARB and VCaP cell-specific TF-binding data...
September 19, 2016: Scientific Reports
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