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prostate cancer genomic sequencing

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https://www.readbyqxmd.com/read/28819847/negative-enrichment-and-isolation-of-circulating-tumor-cells-for-whole-genome-amplification
#1
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
#2
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
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/28794807/prognostic-and-predictive-biomarkers-in-prostate-cancer-latest-evidence-and-clinical-implications
#6
REVIEW
Naoki Terada, Shusuke Akamatsu, Takashi Kobayashi, Takahiro Inoue, Osamu Ogawa, Emmanuel S Antonarakis
Advances in our understanding of the mechanisms driving castration-resistant prostate cancer have promoted the development of several new drugs including androgen receptor-directed therapy and chemotherapy. Concomitant docetaxel treatment at the beginning of hormonal therapy for metastatic prostate cancer has resulted in longer overall survival than with hormonal therapy alone. Elucidating an appropriate treatment sequence using these therapies is important for maximizing clinical benefit in castration-sensitive and castration-resistant prostate cancer patients...
August 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28751446/gene-copy-number-estimation-from-targeted-next-generation-sequencing-of-prostate-cancer-biopsies-analytic-validation-and-clinical-qualification
#7
George Seed, Wei Yuan, Joaquin Mateo, Suzanne Carreira, Claudia Bertan, Maryou Lambros, Gunther Boysen, Roberta Ferraldeschi, Susana Miranda, Ines Figueiredo, Ruth Riisnaes, Mateus Crespo, Daniel Nava Rodrigues, Eric Talevich, Dan R Robinson, Lakshmi P Kunju, Yi-Mi Wu, Robert Lonigro, Shahneen Sandhu, Arul Chinnayan, Johann S de Bono
Abstract <p>Purpose</p> <p>Precise detection of copy number aberrations (CNAs) from tumor biopsies is critically important to the treatment of metastatic prostate cancer. The use of targeted panel next generation sequencing (NGS) is inexpensive, high throughput and easily feasible, allowing single nucleotide variant calls, but CNA estimation from this remains challenging..</p> <p>Experimental Design</p> <p>We evaluated CNVkit for CNA identification from amplicon-based targeted NGS in a cohort of 110 fresh castration resistant prostate cancer biopsies, and used capture based whole exome sequencing (WES), array comparative genomic hybridization (aCGH), and fluorescent in situ hybridization (FISH) to explore the viability of this approach...
July 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28728983/etv4-and-ap1-transcription-factors-form-multivalent-interactions-with-three-sites-on-the-med25-activator-interacting-domain
#8
Simon L Currie, Jedediah J Doane, Kathryn S Evans, Niraja Bhachech, Bethany J Madison, Desmond K W Lau, Lawrence P McIntosh, Jack J Skalicky, Kathleen A Clark, Barbara J Graves
The recruitment of transcriptional cofactors by sequence-specific transcription factors challenges the basis of high affinity and selective interactions. Extending previous studies that the N-terminal activation domain (AD) of ETV5 interacts with Mediator subunit 25 (MED25), we establish that similar, aromatic-rich motifs located both in the AD and in the DNA-binding domain (DBD) of the related ETS factor ETV4 interact with MED25. These ETV4 regions bind MED25 independently, display distinct kinetics, and combine to contribute to a high-affinity interaction of full-length ETV4 with MED25...
July 17, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28728135/prostate-cancer-risk-and-dna-methylation-signatures-in-aging-rats-following-developmental-bpa-exposure-a-dose-response-analysis
#9
Gail S Prins, Shu-Hua Ye, Lynn Birch, Xiang Zhang, Ana Cheong, Han Lin, Esther Calderon-Gierszal, Jacob Groen, Wen-Yang Hu, Shuk-Mei Ho, Richard B van Breemen
BACKGROUND: Previous studies have uncovered heightened prostatic susceptibility to hormone-induced neoplasia from early-life exposure to low-dose bisphenol A (BPA). However, significant data gaps remain that are essential to address for biological relevance and necessary risk assessment. OBJECTIVES: A complete BPA dose-response analysis of prostate lesions across multiple prostatic lobes was conducted that included internal BPA dosimetry, progression to adenocarcinoma with aging and mechanistic connections to epigenetically reprogramed genes...
July 11, 2017: Environmental Health Perspectives
https://www.readbyqxmd.com/read/28721808/molecular-tests-for-the-choice-of-cancer-therapy
#10
Anna P Sokolenko, Evgeny N Imyanitov
There are over a dozen of approved cancer drugs, whose administration is tailored to predictive laboratory tests. The examples include estrogen and progesterone receptor status determination for the use of endocrine therapy, HER2 assessment for the administration of HER2-targeting agents, EGFR and ALK gene testing for lung cancer treatment, BRAF analysis in melanoma, etc. While first predictive tests relied on relatively easy laboratory procedures, more recent developments require rather sophisticated assays...
July 19, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28694034/insertion-and-deletion-derived-tumour-specific-neoantigens-and-the-immunogenic-phenotype-a-pan-cancer-analysis
#11
Samra Turajlic, Kevin Litchfield, Hang Xu, Rachel Rosenthal, Nicholas McGranahan, James L Reading, Yien Ning S Wong, Andrew Rowan, Nnennaya Kanu, Maise Al Bakir, Tim Chambers, Roberto Salgado, Peter Savas, Sherene Loi, Nicolai J Birkbak, Laurent Sansregret, Martin Gore, James Larkin, Sergio A Quezada, Charles Swanton
BACKGROUND: The focus of tumour-specific antigen analyses has been on single nucleotide variants (SNVs), with the contribution of small insertions and deletions (indels) less well characterised. We investigated whether the frameshift nature of indel mutations, which create novel open reading frames and a large quantity of mutagenic peptides highly distinct from self, might contribute to the immunogenic phenotype. METHODS: We analysed whole-exome sequencing data from 5777 solid tumours, spanning 19 cancer types from The Cancer Genome Atlas...
August 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28693295/germline-dna-copy-number-variations-as-potential-prognostic-markers-for-non-muscle-invasive-bladder-cancer-progression
#12
Yoshiaki Yamamoto, Yutaka Suehiro, Atomu Suzuki, Ryosuke Nawata, Yoshihisa Kawai, Ryo Inoue, Hiroshi Hirata, Hiroaki Matsumoto, Takahiro Yamasaki, Kohsuke Sasaki, Hideyasu Matsuyama
Accumulating evidence has suggested that germline DNA copy number variations (CNVs) affect various disorders, including human malignancies. However, the significance of CNVs in non-muscle invasive bladder cancer (NMIBC) remains unclear. The purpose of the present study was to identify the role of CNVs in NMIBC. Array comparative genomic hybridization (CGH) analysis was performed to search for candidate CNVs associated with NMIBC susceptibility. Quantitative polymerase chain reaction was carried out to evaluate CNVs associated with patient outcome in 189 NMIBC cases...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28641312/impact-of-novel-mir-145-3p-regulatory-networks-on-survival-in-patients-with-castration-resistant-prostate-cancer
#13
Yusuke Goto, Akira Kurozumi, Takayuki Arai, Nijiro Nohata, Satoko Kojima, Atsushi Okato, Mayuko Kato, Kazuto Yamazaki, Yasuo Ishida, Yukio Naya, Tomohiko Ichikawa, Naohiko Seki
BACKGROUND: Despite recent advancements, metastatic castration-resistant prostate cancer (CRPC) is not considered curative. Novel approaches for identification of therapeutic targets of CRPC are needed. METHODS: Next-generation sequencing revealed 945-1248 miRNAs from each lethal mCRPC sample. We constructed miRNA expression signatures of CRPC by comparing the expression of miRNAs between CRPC and normal prostate tissue or hormone-sensitive prostate cancer (HSPC)...
July 25, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28623072/commentary-on-integrative-clinical-genomics-of-advanced-prostate-cancer-robinson-d-van-allen-em-wu-ym-schultz-n-lonigro-rj-mosquera-jm-montgomery-b-taplin-me-pritchard-cc-attard-g-beltran-h-abida-w-bradley-rk-vinson-j-cao-x-vats-p-kunju-lp-hussain-m-feng-fy
#14
Stephen J Freedland, William J Aronson
Toward development of a precision medicine framework for metastatic, castration-resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct prospective whole-exome and transcriptome sequencing of bone or soft tissue tumor biopsies from a cohort of 150 mCRPC affected individuals. Aberrations of AR, ETS genes, TP53, and PTEN were frequent (40%-60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer. We identified new genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin, and ZBTB16/PLZF...
June 13, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28618396/vitamin-d-receptor-binding-site-variants-affect-prostate-cancer-progression
#15
Victor C Lin, Shu-Pin Huang, Huei-Ju Ting, Wen-Lung Ma, Chia-Cheng Yu, Chao-Yuan Huang, Hsin-Ling Yin, Tsung-Yi Huang, Cheng-Hsueh Lee, Ta-Yuan Chang, Te-Ling Lu, Bo-Ying Bao
Vitamin D is an important modulator of cellular proliferation through the vitamin D receptor (VDR) that binds to DNA in the regulatory sequences of target genes. We hypothesized that single nucleotide polymorphisms (SNPs) in VDR-binding sites might affect target gene expression and influence the progression of prostate cancer. Using a genome-wide prediction database, 62 SNPs in VDR-binding sites were selected for genotyping in 515 prostate cancer patients and the findings were replicated in an independent cohort of 411 patients...
May 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28614298/erf-mutations-reveal-a-balance-of-ets-factors-controlling-prostate-oncogenesis
#16
Rohit Bose, Wouter R Karthaus, Joshua Armenia, Wassim Abida, Phillip J Iaquinta, Zeda Zhang, John Wongvipat, Elizabeth V Wasmuth, Neel Shah, Patrick S Sullivan, Michael G Doran, Ping Wang, Anna Patruno, Yilin Zhao, Deyou Zheng, Nikolaus Schultz, Charles L Sawyers
Half of all prostate cancers are caused by the TMPRSS2-ERG gene-fusion, which enables androgens to drive expression of the normally silent E26 transformation-specific (ETS) transcription factor ERG in prostate cells. Recent genomic landscape studies of such cancers have reported recurrent point mutations and focal deletions of another ETS member, the ETS2 repressor factor ERF. Here we show these ERF mutations cause decreased protein stability and mostly occur in tumours without ERG upregulation. ERF loss recapitulates the morphological and phenotypic features of ERG gain in normal mouse prostate cells, including expansion of the androgen receptor transcriptional repertoire, and ERF has tumour suppressor activity in the same genetic background of Pten loss that yields oncogenic activity by ERG...
June 29, 2017: Nature
https://www.readbyqxmd.com/read/28611215/genome-wide-crispr-screen-identifies-hnrnpl-as-a-prostate-cancer-dependency-regulating-rna-splicing
#17
Teng Fei, Yiwen Chen, Tengfei Xiao, Wei Li, Laura Cato, Peng Zhang, Maura B Cotter, Michaela Bowden, Rosina T Lis, Shuang G Zhao, Qiu Wu, Felix Y Feng, Massimo Loda, Housheng Hansen He, X Shirley Liu, Myles Brown
Alternative RNA splicing plays an important role in cancer. To determine which factors involved in RNA processing are essential in prostate cancer, we performed a genome-wide CRISPR/Cas9 knockout screen to identify the genes that are required for prostate cancer growth. Functional annotation defined a set of essential spliceosome and RNA binding protein (RBP) genes, including most notably heterogeneous nuclear ribonucleoprotein L (HNRNPL). We defined the HNRNPL-bound RNA landscape by RNA immunoprecipitation coupled with next-generation sequencing and linked these RBP-RNA interactions to changes in RNA processing...
June 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28573914/treatment-strategies-for-dna-repair-deficient-prostate-cancer
#18
REVIEW
Benjamin A Teply, Emmanuel S Antonarakis
Common recurrent genetic alterations have been identified in prostate cancer through comprehensive sequencing efforts, and the prevalence of mutations in DNA repair pathway genes in patients with advanced and metastatic disease approaches 20-25%. Identification of these underlying DNA repair defects may present unique treatment opportunities for patients, both in terms of standard-of-care treatments and selected investigational agents. Areas covered: We review our current understanding of the genomic landscape of prostate cancer, with special attention to alterations in DNA repair pathway genes in metastatic castration-resistant disease...
August 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28540598/parp-inhibitors-in-prostate-cancer
#19
REVIEW
Praveen Ramakrishnan Geethakumari, Matthew J Schiewer, Karen E Knudsen, Wm Kevin Kelly
The genomic landscape of metastatic prostate cancer (mPCa) reveals that up to 90% of patients harbor actionable mutations and >20% have somatic DNA repair gene defects (DRD). This provides the therapeutic rationale of PARP inhibition (PARPi) to achieve "synthetic lethality" in treating this fatal disease. Clinical trials with PARP inhibitors have shown significant response rates up to 88% for PCa patients having DRD like BRCA1/2 or ATM mutations. The FDA has awarded "breakthrough designation" to develop the PARPi olaparib in treating this subset of metastatic PCa patients...
June 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28515055/exome-sequencing-of-african-american-prostate-cancer-reveals-loss-of-function-erf-mutations
#20
Franklin W Huang, Juan Miguel Mosquera, Andrea Garofalo, Coyin Oh, Maria Baco, Ali Amin-Mansour, Bokang Rabasha, Samira Bahl, Stephanie A Mullane, Brian D Robinson, Saud Aldubayan, Francesca Khani, Beerinder Karir, Eejung Kim, Jeremy Chimene-Weiss, Matan Hofree, Alessandro Romanel, Joseph R Osborne, Jong Wook Kim, Gissou Azabdaftari, Anna Woloszynska-Read, Karen Sfanos, Angelo M De Marzo, Francesca Demichelis, Stacey Gabriel, Eliezer M Van Allen, Jill Mesirov, Pablo Tamayo, Mark A Rubin, Isaac J Powell, Levi A Garraway
African-American men have the highest incidence and mortality from prostate cancer. Whether a biological basis exists for this disparity remains unclear. Exome sequencing (n=102) and targeted validation (n = 90) of localized primary hormone-naïve prostate cancer in African-American men identified several gene mutations not previously observed in this context, including recurrent loss-of-function mutations in ERF, an ETS transcriptional repressor, in 5% of cases. Analysis of existing prostate cancer cohorts revealed ERF deletions in 3% of primary prostate cancers and mutations or deletions in ERF in 3-5% of lethal castration-resistant prostate cancers...
May 17, 2017: Cancer Discovery
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