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Oncogenomics

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https://www.readbyqxmd.com/read/28805821/opposing-effects-of-cancer-type-specific-spop-mutants-on-bet-protein-degradation-and-sensitivity-to-bet-inhibitors
#1
Hana Janouskova, Geniver El Tekle, Elisa Bellini, Namrata D Udeshi, Anna Rinaldi, Anna Ulbricht, Tiziano Bernasocchi, Gianluca Civenni, Marco Losa, Tanya Svinkina, Craig M Bielski, Gregory V Kryukov, Luciano Cascione, Sara Napoli, Radoslav I Enchev, David G Mutch, Michael E Carney, Andrew Berchuck, Boris J N Winterhoff, Russell R Broaddus, Peter Schraml, Holger Moch, Francesco Bertoni, Carlo V Catapano, Matthias Peter, Steven A Carr, Levi A Garraway, Peter J Wild, Jean-Philippe P Theurillat
It is generally assumed that recurrent mutations within a given cancer driver gene elicit similar drug responses. Cancer genome studies have identified recurrent but divergent missense mutations affecting the substrate-recognition domain of the ubiquitin ligase adaptor SPOP in endometrial and prostate cancers. The therapeutic implications of these mutations remain incompletely understood. Here we analyzed changes in the ubiquitin landscape induced by endometrial cancer-associated SPOP mutations and identified BRD2, BRD3 and BRD4 proteins (BETs) as SPOP-CUL3 substrates that are preferentially degraded by endometrial cancer-associated SPOP mutants...
August 14, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28754634/an-androgen-regulated-mir-2909-modulates-tgf%C3%AE-signalling-through-ar-mir-2909-axis-in-prostate-cancer
#2
Shiekh Gazalla Ayub, Deepak Kaul, Taha Ayub
In recent years, microRNAs (miRNAs) have emerged as promising biomarkers for PCa diagnosis and prognosis. miR-2909 is a novel miRNA that can regulate immunogenomics and oncogenomics. The present study investigated the role of miR-2909 in the pathogenesis of PCa and the potential signalling pathways through which it operates. We have identified miR-2909 as a novel mediator of androgen/androgen receptor (AR) signalling that enhances the proliferation potential of PCa cells and assists in cancer survival under reduced androgen levels...
July 25, 2017: Gene
https://www.readbyqxmd.com/read/28621265/improving-radiotherapy-in-cancer-treatment-promises-and-challenges
#3
REVIEW
Helen H W Chen, Macus Tien Kuo
Effective radiotherapy for cancer has relied on the promise of maximally eradicating tumor cells while minimally killing normal cells. Technological advancement has provided state-of-the-art instrumentation that enables delivery of radiotherapy with great precision to tumor lesions with substantial reduced injury to normal tissues. Moreover, better understanding of radiobiology, particularly the mechanisms of radiation sensitivity and resistance in tumor lesions and toxicity in normal tissues, has improved the treatment efficacy of radiotherapy...
June 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28546995/the-cost-and-cost-trajectory-of-whole-genome-analysis-guiding-treatment-of-patients-with-advanced-cancers
#4
Deirdre Weymann, Janessa Laskin, Robyn Roscoe, Kasmintan A Schrader, Stephen Chia, Stephen Yip, Winson Y Cheung, Karen A Gelmon, Aly Karsan, Daniel J Renouf, Marco Marra, Dean A Regier
BACKGROUND: Limited data exist on the real-world costs of applying whole-genome analysis (WGA) in a clinical setting. We estimated the costs of applying WGA to guide treatments for patients with advanced cancers and characterized how costs evolve over time. METHODS: The setting is the British Columbia Cancer Agency Personalized OncoGenomics (POG) program in British Columbia, Canada. Cost data were obtained for patients who enrolled in the program from 2012 to 2015...
May 2017: Molecular Genetics & Genomic Medicine
https://www.readbyqxmd.com/read/28498363/a-novel-microrna-regulator-of-prostate-cancer-epithelial-mesenchymal-transition
#5
Nathan Bucay, Divya Bhagirath, Kirandeep Sekhon, Thao Yang, Shinichiro Fukuhara, Shahana Majid, Varahram Shahryari, ZLaura Tabatabai, Kirsten L Greene, Yutaka Hashimoto, Marisa Shiina, Soichiro Yamamura, Yuichiro Tanaka, Guoren Deng, Rajvir Dahiya, Sharanjot Saini
The most frequent alteration in the prostate oncogenome is loss of chromosome (chr) 8p21 that has been associated with loss of NKX3.1 homeobox gene. Chr8p21 deletions increase significantly with tumor grade and are associated with poor prognosis in prostate cancer (PCa), suggesting critical involvement of this region in tumor progression. Recent studies suggest that apart from NKX3.1, this region harbors alternative tumor suppressors that are yet undefined. We proposed a novel, paradigm shifting hypothesis that this locus is associated with a miRNA gene cluster-miR-3622a/b- that plays a crucial suppressive role in PCa...
May 12, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28463229/comparative-oncogenomics-identifies-tyrosine-kinase-fes-as-a-tumor-suppressor-in-melanoma
#6
Michael Olvedy, Julie C Tisserand, Flavie Luciani, Bram Boeckx, Jasper Wouters, Sophie Lopez, Florian Rambow, Sara Aibar, Bernard Thienpont, Jasmine Barra, Corinna Köhler, Enrico Radaelli, Sophie Tartare-Deckert, Stein Aerts, Patrice Dubreuil, Joost J van den Oord, Diether Lambrechts, Paulo De Sepulveda, Jean-Christophe Marine
Identification and functional validation of oncogenic drivers are essential steps toward advancing cancer precision medicine. Here, we have presented a comprehensive analysis of the somatic genomic landscape of the widely used BRAFV600E- and NRASQ61K-driven mouse models of melanoma. By integrating the data with publically available genomic, epigenomic, and transcriptomic information from human clinical samples, we confirmed the importance of several genes and pathways previously implicated in human melanoma, including the tumor-suppressor genes phosphatase and tensin homolog (PTEN), cyclin dependent kinase inhibitor 2A (CDKN2A), LKB1, and others...
June 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28179585/oncogenomic-disruptions-in-arsenic-induced-carcinogenesis
#7
REVIEW
Adam P Sage, Brenda C Minatel, Kevin W Ng, Greg L Stewart, Trevor J B Dummer, Wan L Lam, Victor D Martinez
Chronic exposure to arsenic affects more than 200 million people worldwide, and has been associated with many adverse health effects, including cancer in several organs. There is accumulating evidence that arsenic biotransformation, a step in the elimination of arsenic from the human body, can induce changes at a genetic and epigenetic level, leading to carcinogenesis. At the genetic level, arsenic interferes with key cellular processes such as DNA damage-repair and chromosomal structure, leading to genomic instability...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28173755/melanoma-genome-evolution-across-species
#8
Emily R Kansler, Akanksha Verma, Erin M Langdon, Theresa Simon-Vermot, Alexandra Yin, William Lee, Marc Attiyeh, Olivier Elemento, Richard M White
BACKGROUND: Cancer genomes evolve in both space and time, which contributes to the genetic heterogeneity that underlies tumor progression and drug resistance. In human melanoma, identifying mechanistically important events in tumor evolution is hampered due to the high background mutation rate from ultraviolet (UV) light. Cross-species oncogenomics is a powerful tool for identifying these core events, in which transgenically well-defined animal models of cancer are compared to human cancers to identify key conserved alterations...
February 7, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28067315/kank1-inhibits-cell-growth-by-inducing-apoptosis-though-regulating-cxxc5-in-human-malignant-peripheral-nerve-sheath-tumors
#9
Zhibin Cui, Yingjia Shen, Kenny H Chen, Suresh K Mittal, Jer-Yen Yang, GuangJun Zhang
Malignant peripheral nerve sheath tumors (MPNSTs) are a type of rare sarcomas with a poor prognosis due to its highly invasive nature and limited treatment options. Currently there is no targeted-cancer therapy for this type of malignancy. Thus, it is important to identify more cancer driver genes that may serve as targets of cancer therapy. Through comparative oncogenomics, we have found that KANK1 was a candidate tumor suppressor gene (TSG) for human MPNSTs. Although KANK1 is known as a cytoskeleton regulator, its tumorigenic function in MPNSTs remains largely unknown...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28067031/informed-consent-the-case-of-%C3%A2-omics%C3%A2-literacy
#10
Marilyn Hammer
The world of “-omics” is vastly changing the landscape of accelerated research and its translation to patient care. Understanding this complex science, particularly in the world of oncogenomics, can be daunting. Questions arise pertaining to how nurses can best educate patients who are forced to make difficult decisions without fully understanding to what they are consenting. This article follows a patient story that drives home the need to improve -omics literacy.
January 6, 2017: Oncology Nursing Forum
https://www.readbyqxmd.com/read/28050146/personalized-oncogenomics-in-the-management-of-gastrointestinal-carcinomas-early-experiences-from-a-pilot-study
#11
B S Sheffield, B Tessier-Cloutier, H Li-Chang, Y Shen, E Pleasance, K Kasaian, Y Li, S J M Jones, H J Lim, D J Renouf, D G Huntsman, S Yip, J Laskin, M Marra, D F Schaeffer
BACKGROUND: Gastrointestinal carcinomas are genomically complex cancers that are lethal in the metastatic setting. Whole-genome and transcriptome sequencing allow for the simultaneous characterization of multiple oncogenic pathways. METHODS: We report 3 cases of metastatic gastrointestinal carcinoma in patients enrolled in the Personalized Onco-Genomics program at the BC Cancer Agency. Real-time genomic profiling was combined with clinical expertise to diagnose a carcinoma of unknown primary, to explore treatment response to bevacizumab in a colorectal cancer, and to characterize an appendiceal adenocarcinoma...
December 2016: Current Oncology
https://www.readbyqxmd.com/read/27997009/-genomics-of-lung-adenocarcinoma-pathogenetic-significance-and-clinical-applications
#12
Raffaele Palmirotta, Silvana Acquafredda, Antonella Argentiero, Claudia Carella, Laura Lanotte, Nicla Pappagallo, Davide Quaresmini, Franco Silvestris
Diagnostic and therapeutic approaches to non small cell lung cancer (NSCLC), especially adenocarcinoma, have recently undergone dramatic evolution according to the tremendous amount of molecular data collected on this cancer. In fact, the application of oncogenomics has identified novel molecular subtypes of NSCLC and led the way to diagnostic criteria based on the expression of specific genetic alterations that can provide prognostic and specific indications to the molecular targeted therapies. In NSCLC, several genes show "driver" molecular alterations that confer oncogenic potential to progenitor cells through the enrollment of metabolic pathways critical for cell proliferation and tumor development...
December 2016: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/27798239/phosphatidylinositol-4-kinase-ii%C3%AE-negatively-regulates-invadopodia-formation-and-suppresses-an-invasive-cellular-phenotype
#13
Ganiyu Olabanji Alli-Balogun, Christina A Gewinner, Ruth Jacobs, Janos Kriston-Vizi, Mark G Waugh, Shane Minogue
The type II phosphatidylinositol 4-kinase (PI4KII) enzymes synthesize the lipid phosphatidylinositol 4-phosphate (PI(4)P), which has been detected at the Golgi complex and endosomal compartments and recruits clathrin adaptors. Despite common mechanistic similarities between the isoforms, the extent of their redundancy is unclear. We found that depletion of PI4KIIα and PI4KIIβ using small interfering RNA led to actin remodeling. Depletion of PI4KIIβ also induced the formation of invadopodia containing membrane type I matrix metalloproteinase (MT1-MMP)...
December 15, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27783941/mek-inhibitors-reverse-growth-of-embryonal-brain-tumors-derived-from-oligoneural-precursor-cells
#14
Katarzyna Modzelewska, Elena F Boer, Timothy L Mosbruger, Daniel Picard, Daniela Anderson, Rodney R Miles, Mitchell Kroll, William Oslund, Theodore J Pysher, Joshua D Schiffman, Randy Jensen, Cicely A Jette, Annie Huang, Rodney A Stewart
Malignant brain tumors are the leading cause of cancer-related deaths in children. Primitive neuroectodermal tumors of the CNS (CNS-PNETs) are particularly aggressive embryonal tumors of unknown cellular origin. Recent genomic studies have classified CNS-PNETs into molecularly distinct subgroups that promise to improve diagnosis and treatment; however, the lack of cell- or animal-based models for these subgroups prevents testing of rationally designed therapies. Here, we show that a subset of CNS-PNETs co-express oligoneural precursor cell (OPC) markers OLIG2 and SOX10 with coincident activation of the RAS/MAPK (mitogen-activated protein kinase) pathway...
October 25, 2016: Cell Reports
https://www.readbyqxmd.com/read/27746730/using-pharmacogenomic-databases-for-discovering-patient-target-genes-and-small-molecule-candidates-to-cancer-therapy
#15
José E Belizário, Beatriz A Sangiuliano, Marcela Perez-Sosa, Jennifer M Neyra, Dayson F Moreira
With multiple omics strategies being applied to several cancer genomics projects, researchers have the opportunity to develop a rational planning of targeted cancer therapy. The investigation of such numerous and diverse pharmacogenomic datasets is a complex task. It requires biological knowledge and skills on a set of tools to accurately predict signaling network and clinical outcomes. Herein, we describe Web-based in silico approaches user friendly for exploring integrative studies on cancer biology and pharmacogenomics...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27697861/sik2-restricts-autophagic-flux-to-support-triple-negative-breast-cancer-survival
#16
Kimberly E Maxfield, Jennifer Macion, Hariprasad Vankayalapati, Angelique W Whitehurst
Triple-negative breast cancer (TNBC) is a highly heterogeneous disease with multiple, distinct molecular subtypes that exhibit unique transcriptional programs and clinical progression trajectories. Despite knowledge of the molecular heterogeneity of the disease, most patients are limited to generic, indiscriminate treatment options: cytotoxic chemotherapy, surgery, and radiation. To identify new intervention targets in TNBC, we used large-scale, loss-of-function screening to identify molecular vulnerabilities among different oncogenomic backgrounds...
December 15, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27611943/novel-tumor-suppressor-microrna-at-frequently-deleted-chromosomal-region-8p21-regulates-epidermal-growth-factor-receptor-in-prostate-cancer
#17
Nathan Bucay, Kirandeep Sekhon, Shahana Majid, Soichiro Yamamura, Varahram Shahryari, Z Laura Tabatabai, Kirsten Greene, Yuichiro Tanaka, Rajvir Dahiya, Guoren Deng, Sharanjot Saini
Genomic loss of chromosome (chr) 8p21 region, containing prostate-specific NKX3.1 gene, is a frequent alteration of the prostate cancer (PCa) oncogenome. We propose a novel, paradigm shifting hypothesis that this frequently deleted locus is also associated with a cluster of microRNA genes- miR-3622a/b- that are lost in PCa and play an important mechanistic role in progression and metastasis. In this study, we demonstrate the role of miR-3622b in prostate cancer. Expression analyses in a cohort of PCa clinical specimens and cell lines show that miR-3622b expression is frequently lost in prostate cancer...
October 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27165352/genomic-approaches-to-zebrafish-cancer
#18
REVIEW
Richard M White
The zebrafish has emerged as an important model for studying cancer biology. Identification of DNA, RNA and chromatin abnormalities can give profound insight into the mechanisms of tumorigenesis and the there are many techniques for analyzing the genomes of these tumors. Here, I present an overview of the available technologies for analyzing tumor genomes in the zebrafish, including array based methods as well as next-generation sequencing technologies. I also discuss the ways in which zebrafish tumor genomes can be compared to human genomes using cross-species oncogenomics, which act to filter genomic noise and ultimately uncover central drivers of malignancy...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27148575/lessons-learned-from-the-application-of-whole-genome-analysis-to-the-treatment-of-patients-with-advanced-cancers
#19
Janessa Laskin, Steven Jones, Samuel Aparicio, Stephen Chia, Carolyn Ch'ng, Rebecca Deyell, Peter Eirew, Alexandra Fok, Karen Gelmon, Cheryl Ho, David Huntsman, Martin Jones, Katayoon Kasaian, Aly Karsan, Sreeja Leelakumari, Yvonne Li, Howard Lim, Yussanne Ma, Colin Mar, Monty Martin, Richard Moore, Andrew Mungall, Karen Mungall, Erin Pleasance, S Rod Rassekh, Daniel Renouf, Yaoqing Shen, Jacqueline Schein, Kasmintan Schrader, Sophie Sun, Anna Tinker, Eric Zhao, Stephen Yip, Marco A Marra
Given the success of targeted agents in specific populations it is expected that some degree of molecular biomarker testing will become standard of care for many, if not all, cancers. To facilitate this, cancer centers worldwide are experimenting with targeted "panel" sequencing of selected mutations. Recent advances in genomic technology enable the generation of genome-scale data sets for individual patients. Recognizing the risk, inherent in panel sequencing, of failing to detect meaningful somatic alterations, we sought to establish processes to integrate data from whole-genome analysis (WGA) into routine cancer care...
October 2015: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/27022066/response-to-angiotensin-blockade-with-irbesartan-in-a-patient-with-metastatic-colorectal-cancer
#20
M R Jones, K A Schrader, Y Shen, E Pleasance, C Ch'ng, N Dar, S Yip, D J Renouf, J E Schein, A J Mungall, Y Zhao, R Moore, Y Ma, B S Sheffield, T Ng, S J M Jones, M A Marra, J Laskin, H J Lim
BACKGROUND: A patient suffering from metastatic colorectal cancer, treatment-related toxicity and resistance to standard chemotherapy and radiation was assessed as part of a personalized oncogenomics initiative to derive potential alternative therapeutic strategies. PATIENTS AND METHODS: Whole-genome and transcriptome sequencing was used to interrogate a metastatic tumor refractory to standard treatments of a patient with mismatch repair-deficient metastatic colorectal cancer...
May 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
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