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https://www.readbyqxmd.com/read/30316012/neoantigenic-potential-of-complex-chromosomal-rearrangements-in-mesothelioma
#1
Aaron S Mansfield, Tobias Peikert, James B Smadbeck, Julia B M Udell, Enrique Garcia-Rivera, Laura Elsbernd, Courtney L Erskine, Virginia P Van Keulen, Farhad Kosari, Stephen J Murphy, Hongzheng Ren, Vishnu V Serla, Janet L Schaefer Klein, Giannoula Karagouga, Faye R Harris, Carlos Sosa, Sarah H Johnson, Wendy Nevala, Svetomir N Markovic, Aaron O Bungum, Eric S Edell, Haidong Dong, John C Cheville, Marie Christine Aubry, Jin Jen, George Vasmatzis
INTRODUCTION: Malignant pleural mesothelioma is a disease primarily associated with exposure to the carcinogen asbestos. Whereas other carcinogen-related tumors are associated with a high tumor mutation burden, mesothelioma is not. We sought to resolve this discrepancy. MATERIAL AND METHODS: We used mate-pair (n=22), RNA (n=28) and T cell receptor sequencing along with in silico predictions and immunologic assays to understand how structural variants of chromosomes affect the transcriptome...
October 10, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/30315615/acceleration-of-cancer-science-with-genome-editing-and-related-technologies
#2
REVIEW
Tetsushi Sakuma, Takashi Yamamoto
Genome editing includes various edits of the genome, such as short insertions and deletions, substitutions, and chromosomal rearrangements including inversions, duplications, and translocations. These varieties are based on single or multiple DNA double strand break (DSB)-triggered in cellulo repair machineries. In addition to these "conventional" genome editing strategies, tools enabling customized, site-specific recognition of particular nucleic acid sequences have been coming into wider use, e...
October 13, 2018: Cancer Science
https://www.readbyqxmd.com/read/30315348/association-of-il-36%C3%AE-with-tertiary-lymphoid-structures-and-inflammatory-immune-infiltrates-in-human-colorectal-cancer
#3
Aliyah M Weinstein, Nicolas A Giraldo, Florent Petitprez, Catherine Julie, Laetitia Lacroix, Frédérique Peschaud, Jean-François Emile, Laetitia Marisa, Wolf H Fridman, Walter J Storkus, Catherine Sautès-Fridman
IL-1 family cytokines play a dual role in the gut, with different family members contributing either protective or pathogenic effects. IL-36γ is an IL-1 family cytokine involved in polarizing type-1 immune responses. However, its function in the gut, including in colorectal cancer pathogenesis, is not well appreciated. In a murine model of colon carcinoma, IL-36γ controls tertiary lymphoid structure formation and promotes a type-1 immune response concurrently with a decrease in expression of immune checkpoint molecules in the tumor microenvironment...
October 12, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/30314329/identification-of-the-transcription-factor-relationships-associated-with-androgen-deprivation-therapy-response-and-metastatic-progression-in-prostate-cancer
#4
Nitya V Sharma, Kathryn L Pellegrini, Veronique Ouellet, Felipe O Giuste, Selvi Ramalingam, Kenneth Watanabe, Eloise Adam-Granger, Lucresse Fossouo, Sungyong You, Michael R Freeman, Paula Vertino, Karen Conneely, Adeboye O Osunkoya, Dominique Trudel, Anne-Marie Mes-Masson, John A Petros, Fred Saad, Carlos S Moreno
BACKGROUND: Patients with locally advanced or recurrent prostate cancer typically undergo androgen deprivation therapy (ADT), but the benefits are often short-lived and the responses variable. ADT failure results in castration-resistant prostate cancer (CRPC), which inevitably leads to metastasis. We hypothesized that differences in tumor transcriptional programs may reflect differential responses to ADT and subsequent metastasis. RESULTS: We performed whole transcriptome analysis of 20 patient-matched Pre-ADT biopsies and 20 Post-ADT prostatectomy specimens, and identified two subgroups of patients (high impact and low impact groups) that exhibited distinct transcriptional changes in response to ADT...
October 11, 2018: Cancers
https://www.readbyqxmd.com/read/30312732/progression-from-low-to-high-grade-in-a-glioblastoma-model-reveals-the-pivotal-role-of-immunoediting
#5
Irene Appolloni, Francesco Alessandrini, Davide Ceresa, Daniela Marubbi, Eleonora Gambini, Daniele Reverberi, Fabrizio Loiacono, Paolo Malatesta
The mutual reshape of tumor and immune system cells during tumor progression is a widely accepted notion in different cancers including gliomas. The importance of this phenomenon in shaping glioma progression and the mechanisms governing it, however, are not fully elucidated. Taking advantage of a well-characterized in vivo glioma model we performed an analysis of glioma cells transcriptomes at different stages of progression and unveiled the reorganization of glioma-immune system interactions. Specifically, we show that the inability of low-grade glioma cells to orthotopically graft in syngeneic immunocompetent mice, positively correlates with the abundance of infiltrating lymphocytes in donor tumors and with a highly immunostimulatory transcriptional profile...
October 9, 2018: Cancer Letters
https://www.readbyqxmd.com/read/30311656/chl1-expression-differentiates-h%C3%A3-rthle-cell-carcinoma-from-benign-h%C3%A3-rthle-cell-nodules
#6
Wei Li, Shujun Xia, Anna Aronova, Irene M Min, Akanksha Verma, Theresa Scognamiglio, Katherine D Gray, Timothy M Ullmann, Heng Liang, Maureen D Moore, Olivier Elemento, Rasa Zarnegar, Thomas J Fahey
BACKGROUND AND OBJECTIVES: Hürthle cell carcinoma (HCC) is an unusual and relatively rare type of differentiated thyroid cancer. Currently, cytologic analysis of fine-needle aspiration biopsy is limited in distinguishing benign Hürthle cell neoplasms from malignant ones. The aim of this study was to determine whether differences in the expression of specific genes could differentiate HCC from benign Hürthle cell nodules by evaluating differential gene expression in Hürthle cell disease...
October 12, 2018: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/30311166/aso-author-reflections-the-whole-transcriptome-landscape-of-circulating-tumor-cells-in-nonmetastatic-breast-cancer
#7
Julie E Lang, Kirstyn E Brownson
No abstract text is available yet for this article.
October 11, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/30310055/integrative-analysis-of-transcriptomics-and-clinical-data-uncovers-the-tumor-suppressive-activity-of-mitf-in-prostate-cancer
#8
Lorea Valcarcel-Jimenez, Alice Macchia, Natalia Martín-Martín, Ana Rosa Cortazar, Ariane Schaub-Clerigué, Mikel Pujana-Vaquerizo, Sonia Fernández-Ruiz, Isabel Lacasa-Viscasillas, Aida Santos-Martin, Ana Loizaga-Iriarte, Miguel Unda-Urzaiz, Ivana Hermanova, Ianire Astobiza, Mariona Graupera, Julia Starkova, James Sutherland, Rosa Barrio, Ana M Aransay, Arkaitz Carracedo, Verónica Torrano
The dysregulation of gene expression is an enabling hallmark of cancer. Computational analysis of transcriptomics data from human cancer specimens, complemented with exhaustive clinical annotation, provides an opportunity to identify core regulators of the tumorigenic process. Here we exploit well-annotated clinical datasets of prostate cancer for the discovery of transcriptional regulators relevant to prostate cancer. Following this rationale, we identify Microphthalmia-associated transcription factor (MITF) as a prostate tumor suppressor among a subset of transcription factors...
October 11, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/30308519/a-fus-lats1-2-axis-inhibits-hepatocellular-carcinoma-progression-via-activating-hippo-pathway
#9
Le Bao, Lei Yuan, Pengfei Li, Qingyun Bu, Aijun Guo, Hui Zhang, Ning Cui, Bin Liu
BACKGROUND/AIMS: The roles and related mechanisms of RNA binding protein FUS (fused in sarcoma/translocated in liposarcoma) are unclear in numerous cancers, including hepatocellular carcinoma (HCC). METHODS: Quantitative reverse transcription PCR (qRT-PCR), western blot, cell viability, transwell migration and invasion, tumor spheres formation and in vivo tumor formation assays were used to examine the effects of FUS on HCC progression in HuH7 and MHCC97 cells. Additionally, transcriptome analysis based on RNA-sequencing data, qRT-PCR, western blots, luciferase reporter and RNA binding protein immunoprecipitation (RIP) assays were used to explore the LATS1/2 (large tumor suppressor kinases 1/2)-related mechanisms contributing to FUS functions...
October 11, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/30308005/examining-the-contribution-of-smoking-and-hpv-towards-the-etiology-of-oral-cavity-squamous-cell-carcinoma-using-high-throughput-sequencing-a-prospective-observational-study
#10
Andrew P Zammit, Rohit Sinha, Caroline L Cooper, Christopher F L Perry, Ian H Frazer, Zewen K Tuong
Oral cavity Squamous Cell Carcinoma (OCSCC) is a common form of head and neck cancer throughout the developed and developing world. However, the etiology of OCSCC is still unclear. Here, we explored the extent to which tobacco use, Human Papillomavirus (HPV) infection and genetic and transcriptomic changes contributed to the oncogenesis of OCSCC. In a prospective observational study, we analysed fresh tissue biopsies from 45 OCSCC collected from 51 subjects presenting with OCSCC to the Brisbane Head and Neck Clinics between 2013 and 2015...
2018: PloS One
https://www.readbyqxmd.com/read/30307528/a-global-transcriptomic-pipeline-decoding-core-network-of-genes-involved-in-stages-leading-to-acquisition-of-drug-resistance-to-cisplatin-in-osteosarcoma-cells
#11
Divya Niveditha, Sudeshna Mukherjee, Syamantak Majumder, Rajdeep Chowdhury, Shibashish Chowdhury
Motivation: Traditional cancer therapy is focused on eradicating fast proliferating population of tumor cells. However, existing evidences suggest survival of sub-population of cancer cells that can resist chemotherapy by entering a 'persister' state of minimal growth. These cells eventually survive to produce cells resistant to drugs. The identifying of appropriate targets that can eliminate the drug-tolerant "persisters" remains a challenge. Hence, a deeper understanding of the distinctive genetic signatures that lead to resistance is of utmost importance to design an appropriate therapy...
October 11, 2018: Bioinformatics
https://www.readbyqxmd.com/read/30306389/beyond-dna-the-role-of-epigenetics-in-the-premalignant-progression-of-breast-cancer
#12
REVIEW
Rebecca S DeVaux, Jason I Herschkowitz
Ductal Carcinoma in Situ (DCIS) is an early breast cancer lesion that is considered a nonobligate precursor to development of invasive ductal carcinoma (IDC). Although only a small subset of DCIS lesions are predicted to progress into a breast cancer, distinguishing innocuous from minacious DCIS lesions remains a clinical challenge. Thus, patients diagnosed with DCIS will undergo surgery with the potential for radiation and hormone therapy. This has led to a current state of overdiagnosis and overtreatment...
October 10, 2018: Journal of Mammary Gland Biology and Neoplasia
https://www.readbyqxmd.com/read/30305342/a-four-gene-decision-tree-signature-classification-of-triple-negative-breast-cancer-implications-for-targeted-therapeutics
#13
Jelmar Quist, Hasan Mirza, Maggie C U Cheang, Melinda L Telli, Joyce O'Shaughnessy, Christopher J Lord, Andrew N J Tutt, Anita Grigoriadis
The molecular complexity of triple-negative breast cancers (TNBCs) provides a challenge for patient management. We set out to characterise this heterogeneous disease by combining transcriptomics and genomics data, with the aim of revealing convergent pathway dependencies with the potential for treatment intervention. A Bayesian algorithm was used to integrate molecular profiles in two TNBC cohorts, followed by validation using five independent cohorts (n = 1,168), including three clinical trials. A four-gene decision tree signature was identified which robustly classified TNBCs into six subtypes...
October 10, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/30304690/accurate-drug-repositioning-through-non-tissue-specific-core-signatures-from-cancer-transcriptomes
#14
Chi Xu, Daosheng Ai, Shengbao Suo, Xingwei Chen, Yizhen Yan, Yaqiang Cao, Na Sun, Weizhong Chen, Joseph McDermott, Shiqiang Zhang, Yingying Zeng, Jing-Dong Jackie Han
Experimental large-scale screens for drug repositioning are limited by restriction to in vitro conditions and lack of applicability to real human conditions. Here, we developed an in silico screen in human in vivo conditions using a reference of single gene mutations' non-tissue-specific "core transcriptome signatures" (CSs) of 8,476 genes generated from the TCGA database. We developed the core-signature drug-to-gene (csD2G) software to scan 3,546 drug treatment profiles against the reference signatures...
October 9, 2018: Cell Reports
https://www.readbyqxmd.com/read/30304323/survival-associated-alternative-splicing-signatures-in-esophageal-carcinoma
#15
Shuangshuang Mao, Yuan Li, Zhiliang Lu, Yun Che, Shouguo Sun, Jianbing Huang, Yuanyuan Lei, Xinfeng Wang, Chengming Liu, Sufei Zheng, Ruochuan Zang, Ning Li, Jiagen Li, Nan Sun, Jie He
Alternative splicing (AS), a major mechanism for the enhancement of transcriptome and proteome diversity, has been widely demonstrated to be involved in the full spectrum of oncogenic processes. High-throughput sequencing technology and the rapid accumulation of clinical data sets have provided an opportunity to systemically analyze the association between messenger RNA AS variants and patient clinical outcomes. Here, we compared differentially spliced AS transcripts between esophageal carcinoma (ESCA) and non-tumor tissues, profiled genome-wide survival-associated AS events in 87 patients with esophageal adenocarcinoma (EAC) and 79 patients with esophageal squamous cell carcinoma (ESCC) using The Cancer Genome Atlas (TCGA) RNA-seq data set, and constructed predictive models as well as splicing regulation networks by integrated bioinformatic analysis...
October 9, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/30303978/transcriptomics-reveal-potential-vaccine-antigens-and-a-drastic-increase-of-upregulated-genes-during-theileria-parva-development-from-arthropod-to-bovine-infective-stages
#16
Triza Tonui, Pilar Corredor-Moreno, Esther Kanduma, Joyce Njuguna, Moses N Njahira, Steven G Nyanjom, Joana C Silva, Appolinaire Djikeng, Roger Pelle
Theileria parva is a protozoan parasite transmitted by the brown ear tick Rhipicephalus appendiculatus that causes East Coast fever (ECF) in cattle, resulting in substantial economic losses in the regions of southern, eastern and central Africa. The schizont form of the parasite transforms the bovine host lymphocytes into actively proliferating cancer-like cells. However, how T. parva causes bovine host cells to proliferate and maintain a cancerous phenotype following infection is still poorly understood. On the other hand, current efforts to develop improved vaccines have identified only a few candidate antigens...
2018: PloS One
https://www.readbyqxmd.com/read/30302523/foxc2-promotes-epithelial-mesenchymal-transition-and-cisplatin-resistance-of-non-small-cell-lung-cancer-cells
#17
Yuwen He, Hui Xie, Pengjiu Yu, Shunjun Jiang, Li Wei
PURPOSE: Platinum-based drugs, particularly cisplatin (DDP), are used in the treatment of non-small cell lung cancer (NSCLC). However, development of drug resistance remains the major therapeutic barrier in NSCLC. METHODS: The potential cisplatin resistance-related genes were identified from the global transcriptomes of cisplatin-resistant A549/DDP cells using microarray analysis. Gain- and loss-of-function assays were performed to analyze the effects of Forkhead Box Protein C2 (FOXC2) on the in vitro and in vivo sensitivity of NSCLC cells to cisplatin and its possible molecular mechanisms...
October 9, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/30300142/temporal-dynamics-of-wnt-dependent-transcriptome-reveals-an-oncogenic-wnt-myc-ribosome-axis
#18
Babita Madan, Nathan Harmston, Gahyathiri Nallan, Alex Montoya, Peter Faull, Enrico Petretto, David M Virshup
Activating mutations in the Wnt pathway drive a variety of cancers, but the specific targets and pathways activated by Wnt ligands are not fully understood. To bridge this knowledge gap, we performed a comprehensive time-course analysis of Wnt-dependent signaling pathways in an orthotopic model of Wnt-addicted pancreatic cancer, using a PORCN inhibitor currently in clinical trials, and validated key results in additional Wnt-addicted models. The temporal analysis of the drug-perturbed transcriptome demonstrated direct and indirect regulation of greater than 3,500 Wnt activated genes (23% of the transcriptome)...
October 9, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/30299205/integration-of-genomics-high-throughput-drug-screening-and-personalized-xenograft-models-as-a-novel-precision-medicine-paradigm-for-high-risk-pediatric-cancer
#19
Maria Tsoli, Carol Wadham, Mark Pinese, Tim Failes, Swapna Joshi, Emily Mould, Julia X Yin, Velimir Gayevskiy, Amit Kumar, Warren Kaplan, Paul G Ekert, Federica Saletta, Laura Franshaw, Jie Liu, Andrew Gifford, Martin A Weber, Michael Rodriguez, Richard J Cohn, Greg Arndt, Vanessa Tyrrell, Michelle Haber, Toby Trahair, Glenn M Marshall, Kerrie McDonald, Mark J Cowley, David S Ziegler
Pediatric high grade gliomas (HGG) are primary brain malignancies that result in significant morbidity and mortality. One of the challenges in their treatment is inter- and intra-tumoral heterogeneity. Precision medicine approaches have the potential to enhance diagnostic, prognostic and/or therapeutic information. In this case study we describe the molecular characterization of a pediatric HGG and the use of an integrated approach based on genomic, in vitro and in vivo testing to identify actionable targets and treatment options...
October 9, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/30297899/late-stage-tumors-induce-anemia-and-immunosuppressive-extramedullary-erythroid-progenitor-cells
#20
Lintao Zhao, Ran He, Haixia Long, Bo Guo, Qingzhu Jia, Diyuan Qin, Si-Qi Liu, Zhongyu Wang, Tong Xiang, Jue Zhang, Yulong Tan, Jiani Huang, Junying Chen, Fang Wang, Minglu Xiao, Jianbao Gao, Xinxin Yang, Hao Zeng, Xinxin Wang, Chunyan Hu, Peter B Alexander, Alistair L J Symonds, Jia Yu, Yisong Wan, Qi-Jing Li, Lilin Ye, Bo Zhu
Impaired immunity in patients with late-stage cancer is not limited to antitumor responses, as demonstrated by poor vaccination protection and high susceptibility to infection1-3 . This has been largely attributed to chemotherapy-induced impairment of innate immunity, such as neutropenia2 , whereas systemic effects of tumors on hematopoiesis and adoptive immunity remain incompletely understood. Here we observed anemia associated with severe deficiency of CD8+ T cell responses against pathogens in treatment-naive mice bearing large tumors...
October 2018: Nature Medicine
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