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cancer transcriptome

Clarissa Gerhauser, Francesco Favero, Thomas Risch, Ronald Simon, Lars Feuerbach, Yassen Assenov, Doreen Heckmann, Nikos Sidiropoulos, Sebastian M Waszak, Daniel Hübschmann, Alfonso Urbanucci, Etsehiwot G Girma, Vladimir Kuryshev, Leszek J Klimczak, Natalie Saini, Adrian M Stütz, Dieter Weichenhan, Lisa-Marie Böttcher, Reka Toth, Josephine D Hendriksen, Christina Koop, Pavlo Lutsik, Sören Matzk, Hans-Jörg Warnatz, Vyacheslav Amstislavskiy, Clarissa Feuerstein, Benjamin Raeder, Olga Bogatyrova, Eva-Maria Schmitz, Claudia Hube-Magg, Martina Kluth, Hartwig Huland, Markus Graefen, Chris Lawerenz, Gervaise H Henry, Takafumi N Yamaguchi, Alicia Malewska, Jan Meiners, Daniela Schilling, Eva Reisinger, Roland Eils, Matthias Schlesner, Douglas W Strand, Robert G Bristow, Paul C Boutros, Christof von Kalle, Dmitry Gordenin, Holger Sültmann, Benedikt Brors, Guido Sauter, Christoph Plass, Marie-Laure Yaspo, Jan O Korbel, Thorsten Schlomm, Joachim Weischenfeldt
Identifying the earliest somatic changes in prostate cancer can give important insights into tumor evolution and aids in stratifying high- from low-risk disease. We integrated whole genome, transcriptome and methylome analysis of early-onset prostate cancers (diagnosis ≤55 years). Characterization across 292 prostate cancer genomes revealed age-related genomic alterations and a clock-like enzymatic-driven mutational process contributing to the earliest mutations in prostate cancer patients. Our integrative analysis identified four molecular subgroups, including a particularly aggressive subgroup with recurrent duplications associated with increased expression of ESRP1, which we validate in 12,000 tissue microarray tumors...
December 10, 2018: Cancer Cell
Amanda Balboni Iniguez, Gabriela Alexe, Emily Jue Wang, Giovanni Roti, Sarvagna Patel, Liying Chen, Samuel Kitara, Amy Conway, Amanda L Robichaud, Björn Stolte, Pratiti Bandopadhayay, Amy Goodale, Sasha Pantel, Yenarae Lee, Dorian M Cheff, Matthew D Hall, Rajarshi Guha, Mindy I Davis, Marie Menard, Nicole Nasholm, William A Weiss, Jun Qi, Rameen Beroukhim, Federica Piccioni, Cory Johannessen, Kimberly Stegmaier
Drug resistance represents a major challenge to achieving durable responses to cancer therapeutics. Resistance mechanisms to epigenetically targeted drugs remain largely unexplored. We used bromodomain and extra-terminal domain (BET) inhibition in neuroblastoma as a prototype to model resistance to chromatin modulatory therapeutics. Genome-scale, pooled lentiviral open reading frame (ORF) and CRISPR knockout rescue screens nominated the phosphatidylinositol 3-kinase (PI3K) pathway as promoting resistance to BET inhibition...
December 10, 2018: Cancer Cell
Joshua W Russo, Steven P Balk
In this issue of Cancer Cell, Gerhauser et al. analyze early-onset prostate cancers, showing roles for androgen receptor-driven rearrangements, an early APOBEC-driven mutational mechanism, and ESRP1 gene duplication. Through integration of whole-genome, transcriptome, and methylome data, they identify high-risk subgroups and develop an algorithm that may predict molecular evolution.
December 10, 2018: Cancer Cell
Jason K Sa, Seung Won Choi, Junfei Zhao, Yeri Lee, Jing Zhang, Doo-Sik Kong, Jung Won Choi, Ho Jun Seol, Jung-Il Lee, Antonio Iavarone, Raul Rabadan, Do-Hyun Nam
Hypermutagenesis refers to marked increase in the number of mutations due to continuous mutagenic process. Hypermutated tumors, have being found in several tumor types, are associated with inherited or acquired alterations in DNA repair pathways. Hypermutation has been observed in a subset of adult glioma patients as a direct result of temozolomide(TMZ)-induced mutagenesis. In present study, we have identified a rare subset of treatment-naïve adult gliomas with de novo hypermutator phenotype and explored the evolution of spontaneous and treatment-induced hypermutagenesis...
December 11, 2018: International Journal of Cancer. Journal International du Cancer
Shib Sankar Bhowmick, Debotosh Bhattacharjee, Luis Rato
BACKGROUND: Identification of differentially expressed genes, i.e., genes whose transcript abundance level differs across different biological or physiological conditions, was indeed a challenging task. However, the inception of transcriptome sequencing (RNA-seq) technology revolutionized the simultaneous measurement of the transcript abundance levels for thousands of genes. OBJECTIVE: In this paper, such next-generation sequencing (NGS) data is used to identify biomarker signatures for several of the most common cancer types (bladder, colon, kidney, brain, liver, lung, prostate, skin, and thyroid) METHODS: Here, the problem is mapped into the comparison of optimization algorithms for selecting a set of genes that lead to the highest classification accuracy of a two-class classification task between healthy and tumor samples...
December 8, 2018: Genes & Genomics
Sang-Ho Kang, Jong-Yeol Lee, Tae-Ho Lee, Soo-Yun Park, Chang-Kug Kim
Adlay (Coix lacryma-jobi) is a tropical grass that has long been used in traditional Chinese medicine and is known for its nutritional benefits. Recent studies have shown that vitamin E compounds in adlay protect against chronic diseases such as cancer and heart disease. However, the molecular basis of adlay's health benefits remains unknown. Here, we generated adlay gene sets by de novo transcriptome assembly using long-read isoform sequencing (Iso-Seq) and short-read RNA-Sequencing (RNA-Seq). The gene sets obtained from Iso-seq and RNA-seq contained 31,177 genes and 57,901 genes, respectively...
2018: PloS One
Li Yin, Yahao Wang, Xueqiang Guo, Cunshuan Xu, Guoying Yu
Background: Liver -cell proliferation occurs in hepatocellular carcinoma (HCC) and liver regeneration (LR). The development and progression of HCC and LR have many similar molecular pathways with very different results. In simple terms, LR is a controllable process of organ recovery and function reconstruction, whereas liver cancer is uncontrollable. Do they share common key pathways and genes? Methods: In this study, the dynamic transcriptome profile at ten time points (0, 2, 6, 12, 24, 30, 36, 72, 120, and 168 hours) during LR in rats after two-thirds hepatectomy and eight stages (normal, cirrhosis without HCC, cirrhosis, low-grade dysplastic, high-grade dysplastic, and very early, early advanced, and very advanced HCC) representing a stepwise carcinogenic process from preneoplastic lesions to end-stage HCC were analyzed in detail...
2018: Cancer Management and Research
Jinyeong Lim, Joo Hyun Park, Annika Baude, Jörg Fellenberg, Jozef Zustin, Florian Haller, Irene Krücken, Hyun Guy Kang, Yoon Jung Park, Christoph Plass, Anders M Lindroth
Mutations of histone variant H3.3 are highly recurrent in childhood glioblastoma and in young adults with Giant Cell Tumor of the Bone (GCTB). The heterozygotic representation of the mutations in the tumors, and with potential histone H3 and H3.3 redundancy, suggest that the mutations are gain-of-function by nature. To address common H3.3 point mutations, we have generated data from GCTB patient samples with H3.3 G34W substitutions and engineered human GFP-tagged H3.3-mutated isogenic cell lines for high throughput data comparisons...
December 11, 2018: Scientific Data
Andrew Dhawan, Jacob G Scott, Adrian L Harris, Francesca M Buffa
microRNAs are key regulators of the human transcriptome across a number of diverse biological processes, such as development, aging and cancer, where particular miRNAs have been identified as tumour suppressive and oncogenic. In this work, we elucidate, in a comprehensive manner, across 15 epithelial cancer types comprising 7316 clinical samples from the Cancer Genome Atlas, the association of miRNA expression and target regulation with the phenotypic hallmarks of cancer. Utilising penalised regression techniques to integrate transcriptomic, methylation and mutation data, we find evidence for a complex map of interactions underlying the relationship of miRNA regulation and the hallmarks of cancer...
December 7, 2018: Nature Communications
Susan Tsai, Laura McOlash, Shuang Jia, Jian Zhang, Pippa Simpson, Mary L Kaldunski, Mohammed Aldakkak, Jenny Grewal, Katie Palen, Michael B Dwinell, Bryon D Johnson, Alexander Mackinnon, Martin J Hessner, Jill A Gershan
BACKGROUND: Despite the accessibility of blood, identification of systemic biomarkers associated with cancer progression has been challenging. The aim of this study was to determine a difference in baseline serum immune signatures in patients that experienced early pancreatic ductal adenocarcinoma (PDAC) metastasis with patients that did not. We hypothesized that immune mediators would differ in the baseline serum of these patient cohorts. To test this hypothesis, novel approaches of systemic immune analysis were performed...
December 7, 2018: Cancer Epidemiology, Biomarkers & Prevention
Olli-Pekka Pulkka, Yemarshet K Gebreyohannes, Agnieszka Wozniak, John Patrick Mpindi, Olli Tynninen, Katherine Icay, Alejandra Cervera, Salla Keskitalo, Astrid Murumägi, Evgeny Kulesskiy, Maria Laaksonen, Krister Wennerberg, Markku Varjosalo, Pirjo M Laakkonen, Rainer Lehtonen, Sampsa Hautaniemi, Olli Kallioniemi, Patrick Schöffski, Harri Sihto, Heikki Joensuu
PURPOSE: Gastrointestinal stromal tumor (GIST) is a common type of soft tissue sarcoma. Imatinib, an inhibitor of KIT, PDFGRA and a few other tyrosine kinases, is highly effective for GIST, but advanced GISTs frequently progress on imatinib and other approved tyrosine kinase inhibitors. We investigated phosphodiesterase 3 (PDE3) as a potential therapeutic target in GIST cell lines and xenograft models. EXPERIMENTAL DESIGN: The GIST gene expression profile was interrogated in the MediSapiens IST Online transcriptome database comprising of human tissue and cancer samples, and PDE3A and PDE3B expression was studied using immunohistochemistry on tissue microarrays (TMAs) consisting of 630 formalin-fixed human tissue samples...
December 7, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Miaomiao Ruan, Jiying Liu, Xueyang Ren, Chu Li, Allan Z Zhao, Lin Li, Haiyuan Yang, Yifan Dai, Ying Wang
Glioblastoma (GBM) is a typical malignant tumor, and there are no effective drugs capable of improving patient survival. Docosahexaenoic acid (DHA), a nutrient essential to animal health and neurodevelopment, exerts an anticancer effect in several types of cancer. However, the function of DHA in GBM is still unclear. Here, we showed that DHA could repress the migration and invasion of GBM U251 cells and promote their apoptosis in a dose- and time-dependent manner, indicating that DHA has an anticancer effect on GBM cells...
November 22, 2018: Journal of the Neurological Sciences
Steffen Nielsen, Niels Bassler, Leszek Grzanka, Louise Laursen, Jan Swakon, Pawel Olko, Christian Nicolaj Andreassen, Jan Alsner, Brita Sørensen
PURPOSE: To identify differential cellular responses following proton and photon irradiation by comparing transcriptomes of primary fibroblasts irradiated with either radiation type. METHODS AND MATERIALS: A panel of primary dermal fibroblast cultures were irradiated with low and higher LET proton beams. Cobalt-60 photon irradiation was used as reference. Dose was delivered in 3 fractions x 3.5 Gy(RBE) using a RBE of 1.1 for proton doses. Cells were harvested 2 hours after the final fraction was delivered and RNA was purified...
December 6, 2018: International Journal of Radiation Oncology, Biology, Physics
Li-Shu Zhang, Xunlei Kang, Jianming Lu, Yuannyu Zhang, Xiaofeng Wu, Guojin Wu, Junke Zheng, Rubina Tuladhar, Heping Shi, Qiaoling Wang, Lorraine Morlock, Huiyu Yao, Lily Jun-Shen Huang, Pascal Maire, James Kim, Noelle Williams, Jian Xu, Chuo Chen, Cheng Cheng Zhang, Lawrence Lum
BACKGROUND: Chromosomal translocation-induced expression of the chromatin modifying oncofusion protein MLL-AF9 promotes acute myelocytic leukemia (AML). Whereas WNT/β-catenin signaling has previously been shown to support MLL-AF9-driven leukemogenesis, the mechanism underlying this relationship remains unclear. METHODS: We used two novel small molecules targeting WNT signaling as well as a genetically modified mouse model that allow targeted deletion of the WNT protein chaperone Wntless (WLS) to evaluate the role of WNT signaling in AML progression...
December 6, 2018: EBioMedicine
Jing Li, Tao Yu, Mingxia Yan, Xiao Zhang, Li Liao, Miaoxin Zhu, Hechun Lin, Hongyu Pan, Ming Yao
E3 ubiquitin ligases, which are key enzymes in the ubiquitin proteasome system, catalyze the ubiquitination of proteins to target them for proteasomal degradation. Emerging evidence suggests that E3 ubiquitin ligases play important roles in the development and progression of lung cancer. In our study, we characterized the gene expression landscape of lung cancer using data obtained from TCGA to explore the changes in E3 ubiquitin ligase containing the regulators of E3 ubiquitin ligase activity. Overall, most gene expression changes occurred in NSCLC tissues compared with adjacent normal ones...
December 4, 2018: Experimental Cell Research
Guang'an Xiao, Jingjing Yao, Depei Kong, Chen Ye, Rui Chen, Li Li, Tao Zeng, Liujun Wang, Wei Zhang, Xiaolei Shi, Tie Zhou, Jing Li, Yue Wang, Chuan Liang Xu, Junfeng Jiang, Yinghao Sun
BACKGROUND: The link between prostate cancer (PCa) development and aberrant expression of genes located on the Y chromosome remains unclear. OBJECTIVE: To identify Y-chromosomal long noncoding RNAs (lncRNAs) with critical roles in PCa and to clarify the corresponding mechanisms. DESIGN, SETTING, AND PARTICIPANTS: Aberrantly expressed lncRNAs on the Y chromosome were identified using transcriptome analysis of PCa clinical samples and cell lines...
December 7, 2018: European Urology
Shashi Kumar Gupta, Ankita Garg, Petros Avramopoulos, Stefan Engelhardt, Katrin Streckfuss-Bömeke, Sandor Batkai, Thomas Thum
Improved therapy of cancer has significantly increased the lifespan of patients. However, cancer survivors face an increased risk of cardiovascular complications due to adverse effects of cancer therapies. The chemotherapy drug doxorubicin is well known to induce myofibril damage and cardiac atrophy. Our aim was to test potential counteracting effects of the pro-hypertrophic miR-212/132 family in doxorubicin-induced cardiotoxicity. In vitro, overexpression of the pro-hypertrophic miR-212/132 cluster in primary rodent and human iPSC-derived cardiomyocytes inhibited doxorubicin-induced toxicity...
November 13, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
F Ng Kee Kwong, A G Nicholson, S Pavlidis, I M Adcock, K F Chung
BACKGROUND: COPD patients are at increased risk of developing non-small cell lung carcinoma that has a worse prognosis. Oxidative stress contributes to carcinogenesis and is increased in COPD patients due to mitochondrial dysfunction. We determined whether mitochondrial dysfunction is a contributing factor to the reduced survival of COPD patients with non-small cell lung carcinoma (NSCLC). METHODS: Using a transcriptomic database and outcome data of 3553 NSCLC samples, we selected mitochondrial-related genes whose levels in the tumour correlated with patient mortality...
December 10, 2018: BMC Cancer
Faezeh Shabani Azim, Hamidreza Houri, Zohreh Ghalavand, Bahram Nikmanesh
Background: The aim of this mini-review is to highlight the potential applications of next-generation sequencing technology to the field of clinical oncology with respect to genetic diagnosis, cancer classification, predictive biomarkers and personalized medicine. Methods: Scientific databases were searched to collect relative data. Results: Effective systematic analysis of whole-genome sequence and whole-exome sequence of tumors, targeted genome profiling, transcriptome sequencing and tumor-normal comparisons can be performed using NGS in order to diagnosis of several types of cancer...
October 2018: Iranian Journal of Public Health
Say Li Kong, Huipeng Li, Joyce A Tai, Elise T Courtois, Huay Mei Poh, Dawn Pingxi Lau, Yu Xuan Haw, Narayanan Gopalakrishna Iyer, Daniel Shao Weng Tan, Shyam Prabhakar, Dave Ruff, Axel M Hillmer
BACKGROUND: The comeasurement of both genomic and transcriptomic signatures in single cells is of fundamental importance to accurately assess how the genetic information correlates with the transcriptomic phenotype. However, existing technologies have low throughput and laborious work flows. METHODS: We developed a new method for concurrent sequencing of the transcriptome and targeted genomic regions (CORTAD-seq) within the same single cell on an automated microfluidic platform...
December 6, 2018: Clinical Chemistry
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