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prostate cancer genomic sequencing

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https://www.readbyqxmd.com/read/28424341/alterations-in-three-dimensional-organization-of-the-cancer-genome-and-epigenome
#1
Joanna Achinger-Kawecka, Phillippa C Taberlay, Susan J Clark
The structural and functional basis of the genome is provided by the three-dimensional (3D) chromatin state. To enable accurate gene regulation, enhancer elements and promoter regions are brought into close spatial proximity to ensure proper, cell type-specific gene expression. In cancer, genetic and epigenetic processes can deregulate the transcriptional program. To investigate whether the 3D chromatin state is also disrupted in cancer we performed Hi-C chromosome conformation sequencing in normal and prostate cancer cells and compared the chromatin interaction maps with changes to the genome and epigenome...
April 19, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28423598/next-generation-mapping-reveals-novel-large-genomic-rearrangements-in-prostate-cancer
#2
Weerachai Jaratlerdsiri, Eva K F Chan, Desiree C Petersen, Claire Yang, Peter I Croucher, M S Riana Bornman, Palak Sheth, Vanessa M Hayes
Complex genomic rearrangements are common molecular events driving prostate carcinogenesis. Clinical significance, however, has yet to be fully elucidated. Detecting the full range and subtypes of large structural variants (SVs), greater than one kilobase in length, is challenging using clinically feasible next generation sequencing (NGS) technologies. Next generation mapping (NGM) is a new technology that allows for the interrogation of megabase length DNA molecules outside the detection range of single-base resolution NGS...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415558/family-with-sequence-similarity-13c-fam13c-overexpression-is-an-independent-prognostic-marker-in-prostate-cancer
#3
Christoph Burdelski, Laura Borcherding, Martina Kluth, Claudia Hube-Magg, Nathaniel Melling, Ronald Simon, Christina Möller-Koop, Philipp Weigand, Sarah Minner, Alexander Haese, Hans Uwe Michl, Maria Christina Tsourlakis, Frank Jacobsen, Andrea Hinsch, Corinna Wittmer, Patrick Lebok, Stefan Steurer, Jakob R Izbicki, Guido Sauter, Till Krech, Franziska Büscheck, Till Clauditz, Thorsten Schlomm, Waldemar Wilczak
FAM13C, a gene with unknown function is included in several mRNA signatures for prostate cancer aggressiveness. To understand the impact of FAM13C on prognosis and its relationship to molecularly defined subsets, we analyzed FAM13C expression by immunohistochemistry on a tissue microarray containing 12,400 prostate cancer specimens. Results were compared to phenotype, ERG status, genomic deletions of 3p, 5q, 6q and PTEN, and biochemical recurrence. FAM13C was detectable in cell nuclei of cancerous and non-neoplastic prostate cells...
March 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413162/whole-genome-sequence-of-the-metastatic-pc3-and-lncap-human-prostate-cancer-cell-lines
#4
Inge Seim, Penny L Jeffery, Patrick B Thomas, Colleen C Nelson, Lisa K Chopin
The bone metastasis-derived PC3 and the lymph node metastasis-derived LNCaP prostate cancer cell lines are widely studied, having been described in thousands of publications over the last four decades. Here, we report short-read whole-genome sequencing and de novo assembly of PC3 (ATCC CRL-1435) and LNCaP (clone FGC; ATCC CRL-1740) at ~70X coverage. A known homozygous mutation in TP53 and homozygous loss of PTEN were robustly identified in the PC3 cell line, whereas the LNCaP cell line exhibited a larger number of putative inactivating somatic point and indel mutations (and in particular loss of stop codon events)...
April 16, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28393575/using-circulating-cell-free-dna-to-monitor-personalized-cancer-therapy
#5
Michael Oellerich, Ekkehard Schütz, Julia Beck, Philipp Kanzow, Piers N Plowman, Glen J Weiss, Philip D Walson
High-quality genomic analysis is critical for personalized pharmacotherapy in patients with cancer. Tumor-specific genomic alterations can be identified in cell-free DNA (cfDNA) from patient blood samples and can complement biopsies for real-time molecular monitoring of treatment, detection of recurrence, and tracking resistance. cfDNA can be especially useful when tumor tissue is unavailable or insufficient for testing. For blood-based genomic profiling, next-generation sequencing (NGS) and droplet digital PCR (ddPCR) have been successfully applied...
April 10, 2017: Critical Reviews in Clinical Laboratory Sciences
https://www.readbyqxmd.com/read/28376164/germline-mutations-in-the-kallikrein-6-region-and-predisposition-for-aggressive-prostate-cancer
#6
Laurent Briollais, Hilmi Ozcelik, Jingxiong Xu, Maciej Kwiatkowski, Emilie Lalonde, Dorota H Sendorek, Neil E Fleshner, Franz Recker, Cynthia Kuk, Ekaterina Olkhov-Mitsel, Tristan Juvet, Ioannis Prassas, John Trachtenberg, Ants Toi, Michael Fraser, Theodorus van der Kwast, Robert G Bristow, Bharati Bapat, Eleftherios P Diamandis, Paul C Boutros, Alexandre R Zlotta
Background: There is a need for markers that can specifically identify individuals at increased risk of harboring aggressive forms of prostate cancer (PCa). Methods: We surveyed the Kallikrein ( KLK ) region ( KLK 1-15) for single-nucleotide polymorphisms (SNPs) associated with aggressive PCa (Gleason Score ≥ 8) in 1858 PCa patients. Discovery cohorts (Swiss arm of the European Randomized Study of Screening for PCa, n = 379; Toronto, Canada, n = 540) and a validation cohort (Prostate, Lung, Colorectal and Ovarian [PLCO] screening trial, n = 939) were analyzed...
April 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28330676/stromal-gene-expression-is-predictive-for-metastatic-primary-prostate-cancer
#7
Fan Mo, Dong Lin, Mandeep Takhar, Varune Rohan Ramnarine, Xin Dong, Robert H Bell, Stanislav V Volik, Kendric Wang, Hui Xue, Yuwei Wang, Anne Haegert, Shawn Anderson, Sonal Brahmbhatt, Nicholas Erho, Xinya Wang, Peter W Gout, James Morris, R Jeffrey Karnes, Robert B Den, Eric A Klein, Edward M Schaeffer, Ashley Ross, Shancheng Ren, S Cenk Sahinalp, Yingrui Li, Xun Xu, Jun Wang, Jian Wang, Martin E Gleave, Elai Davicioni, Yinghao Sun, Yuzhuo Wang, Colin C Collins
BACKGROUND: Clinical grading systems using clinical features alongside nomograms lack precision in guiding treatment decisions in prostate cancer (PCa). There is a critical need for identification of biomarkers that can more accurately stratify patients with primary PCa. OBJECTIVE: To identify a robust prognostic signature to better distinguish indolent from aggressive prostate cancer (PCa). DESIGN, SETTING, AND PARTICIPANTS: To develop the signature, whole-genome and whole-transcriptome sequencing was conducted on five PCa patient-derived xenograft (PDX) models collected from independent foci of a single primary tumor and exhibiting variable metastatic phenotypes...
March 19, 2017: European Urology
https://www.readbyqxmd.com/read/28323658/changing-face-of-metastatic-prostate-cancer-the-law-of-diminishing-returns-holds-true
#8
Ulka N Vaishampayan
PURPOSE OF REVIEW: Prostate cancer presents with a multitude of faces. It ranges from localized cancers staying quiescent for many years during active surveillance to the raging diffuse liver metastases causing terminal disease. The incidence of metastatic disease is increasing. This review will highlight some of the recent developments as well as ongoing challenges of managing advanced prostate cancer. RECENT FINDINGS: Significant strides are being made in managing metastatic prostate cancer...
March 18, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28319090/a-single-copy-sleeping-beauty-transposon-mutagenesis-screen-identifies-new-pten-cooperating-tumor-suppressor-genes
#9
Jorge de la Rosa, Julia Weber, Mathias Josef Friedrich, Yilong Li, Lena Rad, Hannes Ponstingl, Qi Liang, Sandra Bernaldo de Quirós, Imran Noorani, Emmanouil Metzakopian, Alexander Strong, Meng Amy Li, Aurora Astudillo, María Teresa Fernández-García, María Soledad Fernández-García, Gary J Hoffman, Rocío Fuente, George S Vassiliou, Roland Rad, Carlos López-Otín, Allan Bradley, Juan Cadiñanos
The overwhelming number of genetic alterations identified through cancer genome sequencing requires complementary approaches to interpret their significance and interactions. Here we developed a novel whole-body insertional mutagenesis screen in mice, which was designed for the discovery of Pten-cooperating tumor suppressors. Toward this aim, we coupled mobilization of a single-copy inactivating Sleeping Beauty transposon to Pten disruption within the same genome. The analysis of 278 transposition-induced prostate, breast and skin tumors detected tissue-specific and shared data sets of known and candidate genes involved in cancer...
March 20, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28275218/epigenomic-regulation-of-androgen-receptor-signaling-potential-role-in-prostate-cancer-therapy
#10
REVIEW
Vito Cucchiara, Joy C Yang, Vincenzo Mirone, Allen C Gao, Michael G Rosenfeld, Christopher P Evans
Androgen receptor (AR) signaling remains the major oncogenic pathway in prostate cancer (PCa). Androgen-deprivation therapy (ADT) is the principle treatment for locally advanced and metastatic disease. However, a significant number of patients acquire treatment resistance leading to castration resistant prostate cancer (CRPC). Epigenetics, the study of heritable and reversible changes in gene expression without alterations in DNA sequences, is a crucial regulatory step in AR signaling. We and others, recently described the technological advance Chem-seq, a method to identify the interaction between a drug and the genome...
January 16, 2017: Cancers
https://www.readbyqxmd.com/read/28258894/pan-cancer-analysis-of-genomic-sequencing-among-the-elderly
#11
Daniel R Wahl, Paul L Nguyen, Maria Santiago, Kasra Yousefi, Elai Davicioni, Dean A Shumway, Corey Speers, Rohit Mehra, Felix Y Feng, Joseph R Osborne, Daniel E Spratt
PURPOSE: We hypothesized that elderly patients might have age-specific genetic abnormalities yet be underrepresented in currently available sequencing repositories, which could limit the effect of sequencing efforts for this population. METHODS AND MATERIALS: Leveraging The Cancer Genome Atlas (TCGA) data portal, 9 tumor types were analyzed. The frequency distribution of cancer by age was determined and compared with Surveillance, Epidemiology, and End Results data...
January 7, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28228136/circulating-tumor-cells-capture-disease-evolution-in-advanced-prostate-cancer
#12
Justin Lack, Marc Gillard, Maggie Cam, Gladell P Paner, David J VanderWeele
BACKGROUND: Genetic analysis of advanced cancer is limited by availability of representative tissue. Biopsies of prostate cancer metastasized to bone are invasive with low quantity of tumor tissue. The prostate cancer genome is dynamic, however, with temporal heterogeneity requiring repeated evaluation as the disease evolves. Circulating tumor cells (CTCs) offer an alternative, "liquid biopsy", though single CTC sequencing efforts are laborious with high failure rates. METHODS: We performed exome sequencing of matched treatment-naïve tumor tissue, castrate resistant tumor tissue, and pooled CTC samples, and compared mutations identified in each...
February 23, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28139641/reconstructing-metastatic-seeding-patterns-of-human-cancers
#13
Johannes G Reiter, Alvin P Makohon-Moore, Jeffrey M Gerold, Ivana Bozic, Krishnendu Chatterjee, Christine A Iacobuzio-Donahue, Bert Vogelstein, Martin A Nowak
Reconstructing the evolutionary history of metastases is critical for understanding their basic biological principles and has profound clinical implications. Genome-wide sequencing data has enabled modern phylogenomic methods to accurately dissect subclones and their phylogenies from noisy and impure bulk tumour samples at unprecedented depth. However, existing methods are not designed to infer metastatic seeding patterns. Here we develop a tool, called Treeomics, to reconstruct the phylogeny of metastases and map subclones to their anatomic locations...
January 31, 2017: Nature Communications
https://www.readbyqxmd.com/read/28134791/a-tale-of-two-signals-ar-and-wnt-in-development-and-tumorigenesis-of-prostate-and-mammary-gland
#14
REVIEW
Hubert Pakula, Dongxi Xiang, Zhe Li
Prostate cancer (PCa) is one of the most common cancers and among the leading causes of cancer deaths for men in industrialized countries. It has long been recognized that the prostate is an androgen-dependent organ and PCa is an androgen-dependent disease. Androgen action is mediated by the androgen receptor (AR). Androgen deprivation therapy (ADT) is the standard treatment for metastatic PCa. However, almost all advanced PCa cases progress to castration-resistant prostate cancer (CRPC) after a period of ADT...
January 27, 2017: Cancers
https://www.readbyqxmd.com/read/28131897/long-noncoding-rnas-and-sulforaphane-a-target-for-chemoprevention-and-suppression-of-prostate-cancer
#15
Laura M Beaver, Rachael Kuintzle, Alex Buchanan, Michelle W Wiley, Sarah T Glasser, Carmen P Wong, Gavin S Johnson, Jeff H Chang, Christiane V Löhr, David E Williams, Roderick H Dashwood, David A Hendrix, Emily Ho
Long noncoding RNAs (lncRNAs) have emerged as important in cancer development and progression. The impact of diet on lncRNA expression is largely unknown. Sulforaphane (SFN), obtained from vegetables like broccoli, can prevent and suppress cancer formation. Here we tested the hypothesis that SFN attenuates the expression of cancer-associated lncRNAs. We analyzed whole-genome RNA-sequencing data of normal human prostate epithelial cells and prostate cancer cells treated with 15 μM SFN or dimethylsulfoxide. SFN significantly altered expression of ~100 lncRNAs in each cell type and normalized the expression of some lncRNAs that were differentially expressed in cancer cells...
April 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28119368/gleason-score-7-prostate-cancers-emerge-through-branched-evolution-of-clonal-gleason-pattern-3-and-4
#16
Adam G Sowalsky, Haydn T Kissick, Sean Gerrin, Rachel Schaefer, Zheng Xia, Joshua Russo, Mohamed S Arredouani, Glenn J Bubley, Martin G Sanda, Wei Li, Huihui Ye, Steven P Balk
PURPOSE: The molecular features that account for the distinct histology and aggressive biological behavior of Gleason pattern 4 (Gp4) versus Gp3 prostate cancer (PCa), and whether Gp3 tumors progress directly to Gp4, remain to be established. EXPERIMENTAL DESIGN: Whole exome sequencing and transcriptome profiling of laser-capture microdissected adjacent Gp3 and cribiform Gp4 were used to determine the relationship between these entities. RESULTS: Sequencing confirmed that adjacent Gp3 and Gp4 were clonal based on multiple shared genomic alterations...
January 24, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28114882/fugeprior-a-novel-gene-fusion-prioritization-algorithm-based-on-accurate-fusion-structure-analysis-in-cancer-rna-seq-samples
#17
Giulia Paciello, Elisa Ficarra
BACKGROUND: Latest Next Generation Sequencing technologies opened the way to a novel era of genomic studies, allowing to gain novel insights into multifactorial pathologies as cancer. In particular gene fusion detection and comprehension have been deeply enhanced by these methods. However, state of the art algorithms for gene fusion identification are still challenging. Indeed, they identify huge amounts of poorly overlapping candidates and all the reported fusions should be considered for in lab validation clearly overwhelming wet lab capabilities...
January 23, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28112170/microrna-141-suppresses-prostate-cancer-stem-cells-and-metastasis-by-targeting-a-cohort-of-pro-metastasis-genes
#18
Can Liu, Ruifang Liu, Dingxiao Zhang, Qu Deng, Bigang Liu, Hsueh-Ping Chao, Kiera Rycaj, Yoko Takata, Kevin Lin, Yue Lu, Yi Zhong, John Krolewski, Jianjun Shen, Dean G Tang
MicroRNAs play important roles in regulating tumour development, progression and metastasis. Here we show that one of the miR-200 family members, miR-141, is under-expressed in several prostate cancer (PCa) stem/progenitor cell populations in both xenograft and primary patient tumours. Enforced expression of miR-141 in CD44(+) and bulk PCa cells inhibits cancer stem cell properties including holoclone and sphere formation, as well as invasion, and suppresses tumour regeneration and metastasis. Moreover, miR-141 expression enforces a strong epithelial phenotype with a partial loss of mesenchymal phenotype...
January 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28107606/dishevelled-segment-polarity-protein-3-dvl3-a-novel-and-easily-applicable-recurrence-predictor-in-localized-prostate-adenocarcinoma
#19
Pil-Jong Kim, Ji Y Park, Hong-Gee Kim, Yong Mee Cho, Heounjeong Go
OBJECTIVE: To identify new biomarkers for the biochemical recurrence (BCR) of prostate adenocarcinoma. PATIENTS AND METHODS: Clinical information of 500 prostate adenocarcinoma patients and their 152 RNA-sequencing and protein-array data from The Cancer Genome Atlas (TCGA) were separated into a discovery-set and a validation-set. Each dataset was analyzed according to the Gleason grade groups reflecting BCR. The results obtained from the analysis using TCGA dataset were confirmed by immunohistochemistry analyses of the confirmation cohort composed of 395 localized prostate adenocarcinoma patients...
January 20, 2017: BJU International
https://www.readbyqxmd.com/read/28104311/comprehensive-profiling-of-the-androgen-receptor-in-liquid-biopsies-from-castration-resistant-prostate-cancer-reveals-novel-intra-ar-structural-variation-and-splice-variant-expression-patterns
#20
Bram De Laere, Pieter-Jan van Dam, Tom Whitington, Markus Mayrhofer, Emanuela Henao Diaz, Gert Van den Eynden, Jean Vandebroek, Jurgen Del-Favero, Steven Van Laere, Luc Dirix, Henrik Grönberg, Johan Lindberg
BACKGROUND: Expression of the androgen receptor splice variant 7 (AR-V7) is associated with poor response to second-line endocrine therapy in castration-resistant prostate cancer (CRPC). However, a large fraction of nonresponding patients are AR-V7-negative. OBJECTIVE: To investigate if a comprehensive liquid biopsy-based AR profile may improve patient stratification in the context of second-line endocrine therapy. DESIGN, SETTING, AND PARTICIPANTS: Peripheral blood was collected from patients with CRPC (n=30) before initiation of a new line of systemic therapy...
January 16, 2017: European Urology
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