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RNA sequencing Breast Cancer

Wayne O Miles, Antonio Lembo, Angela Volorio, Elena Brachtel, Bin Tian, Dennis Sgroi, Paolo Provero, Nicholas Dyson
Alternative polyadenylation (APA) is a process that changes the post-transcriptional regulation and translation potential of mRNAs via addition or deletion of 3'UTR sequences. To identify post-transcriptional regulatory events affected by APA in breast tumors, tumor datasets were analyzed for recurrent APA events. Motif mapping of the changed 3'UTR region found that APA-mediated removal of Pumilio Regulatory Elements (PRE) was unusually common. Breast tumor sub-type specific APA profiling identified triple-negative breast tumors as having the highest levels of APA...
October 10, 2016: Cancer Research
Pravin Kumar Ankush Jagtap, Divita Garg, Tobias G Kapp, Cindy L Will, Oliver Demmer, Reinhard Luhrmann, Horst Kessler, Michael Sattler
U2AF homology motifs (UHMs) are atypical RNA Recognition Motif (RRM) domains that mediate critical protein-protein interactions during the regulation of alternative pre-mRNA splicing and other processes. The recognition of UHM domains by UHM Ligand Motif (ULM) peptide sequences plays important roles during early steps of spliceosome assembly. Splicing factor 45 kDa (SPF45) is an alternative splicing factor implicated in breast and lung cancer and splicing regulation of apoptosis-linked pre-mRNAs by SPF45 was shown to depend on interactions of its UHM domain with ULM motifs in constitutive splicing factors...
October 18, 2016: Journal of Medicinal Chemistry
Jong-Joo Lee, Mikyoung Kim, Hyoung-Pyo Kim
Special AT-rich sequence binding protein 1 (SATB1) is a nuclear matrix-associated DNA-binding protein that functions as a chromatin organizer. SATB1 is highly expressed in aggressive breast cancer cells and promotes growth and metastasis by reprograming gene expression. Through genome-wide cross-examination of gene expression and histone methylation, we identified SATB1 target genes for which expression is associated with altered epigenetic marks. Among the identified genes, long noncoding RNA urothelial carcinoma-associated 1 (UCA1) was upregulated by SATB1 depletion...
September 29, 2016: BMB Reports
Debora Fumagalli, David Venet, Michail Ignatiadis, Hatem A Azim, Marion Maetens, Françoise Rothé, Roberto Salgado, Ian Bradbury, Lajos Pusztai, Nadia Harbeck, Henry Gomez, Tsai-Wang Chang, Maria Antonia Coccia-Portugal, Serena Di Cosimo, Evandro de Azambuja, Lorena de la Peña, Paolo Nuciforo, Jan C Brase, Jens Huober, José Baselga, Martine Piccart, Sherene Loi, Christos Sotiriou
Importance: In neoadjuvant trials, treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancers with dual HER2 blockade resulted in increased pathologic complete response (pCR) rates compared with each targeted agent alone. Amplification and/or overexpression of HER2 currently remains the only biomarker for therapeutic decisions, but it is insufficient to explain the heterogeneous response to anti-HER2 agents. Objective: To investigate the ability of clinically and biologically relevant genes and gene signatures (GSs) measured by RNA sequencing to predict the efficacy of anti-HER2 agents...
September 29, 2016: JAMA Oncology
Anne A Blanchard, Teresa Zelinski, Jiuyong Xie, Steven Cooper, Carla Penner, Etienne Leygue, Yvonne Myal
BACKGROUND: The claudin 1 tight junction protein, solely responsible for the barrier function of epithelial cells, is frequently down regulated in invasive human breast cancer. The underlying mechanism is largely unknown, and no obvious mutations in the claudin 1 gene (CLDN1) have been identified to date in breast cancer. Since many genes have been shown to undergo deregulation through splicing and mis-splicing events in cancer, the current study was undertaken to investigate the occurrence of transcript variants for CLDN1 in human invasive breast cancer...
2016: PloS One
Luca Malorni, Silvano Piazza, Yari Ciani, Cristina Guarducci, Martina Bonechi, Chiara Biagioni, Christopher D Hart, Roberto Verardo, Angelo Di Leo, Ilenia Migliaccio
Palbociclib is a CDK4/6 inhibitor that received FDA approval for treatment of hormone receptor positive (HR+) HER2 negative (HER2neg) advanced breast cancer. To better personalize patients treatment it is critical to identify subgroups that would mostly benefit from it. We hypothesize that complex alterations of the Retinoblastoma (Rb) pathway might be implicated in resistance to CDK4/6 inhibitors and aim to investigate whether signatures of Rb loss-of-function would identify breast cancer cell lines resistant to palbociclib...
September 13, 2016: Oncotarget
Trung Nghia Vu, Setia Pramana, Stefano Calza, Chen Suo, Donghwan Lee, Yudi Pawitan
Molecular classification of breast cancer into clinically relevant subtypes helps improve prognosis and adjuvant-treatment decisions. The aim of this study is to provide a better characterization of the molecular subtypes by providing a comprehensive landscape of subtype-specific isoforms including coding, long non-coding RNA and microRNA transcripts. Isoform-level expression of all coding and non-coding RNAs is estimated from RNA-sequence data of 1168 breast samples obtained from The Cancer Genome Atlas (TCGA) project...
September 13, 2016: Oncotarget
H Kim, S N Danishmalik, H Hwang, J-I Sin, J Oh, Y Cho, H Lee, M Jeong, S-H Kim, H J Hong
Plasmid DNA-encoded antibodies, or DNA-based monoclonal antibodies (dMAbs), are delivered by intramuscular injection and in vivo electroporation (EP) and are effective in virus neutralization, although they have not been evaluated for tumor gene therapy. Here we investigated whether a dMAb was appropriate for tumor gene therapy. We constructed the expression plasmids coding for the heavy or light chain of a parental murine antibody of Herceptin with the antibody genes codon- and RNA-optimized and fused to the Kozak-IgE leader sequence in pVax1...
September 16, 2016: Cancer Gene Therapy
Preethi Krishnan, Sunita Ghosh, Bo Wang, Mieke Heyns, Kathryn Graham, John R Mackey, Olga Kovalchuk, Sambasivarao Damaraju
One of the most abundant, yet least explored, classes of RNA is the small nucleolar RNAs (snoRNAs), which are well known for their involvement in post-transcriptional modifications of other RNAs. Although snoRNAs were only considered to perform housekeeping functions for a long time, recent studies have highlighted their importance as regulators of gene expression and as diagnostic/prognostic markers. However, the prognostic potential of these RNAs has not been interrogated for breast cancer (BC). The objective of the current study was to identify snoRNAs as prognostic markers for BC...
2016: PloS One
Gema Santamaría Nuñez, Carlos Mario Genes Robles, Christophe Giraudon, Juan Fernando Martínez-Leal, Emmanuel Compe, Frédéric Coin, Pablo Aviles, Carlos María Galmarini, Jean-Marc Egly
We have defined the mechanism of action of lurbinectedin, a marine-derived drug exhibiting a potent antitumor activity across several cancer cell lines and tumor xenografts. This drug, currently undergoing clinical evaluation in ovarian, breast, and small cell lung cancer patients, inhibits the transcription process through (i) its binding to CG-rich sequences, mainly located around promoters of protein-coding genes; (ii) the irreversible stalling of elongating RNA polymerase II (Pol II) on the DNA template and its specific degradation by the ubiquitin/proteasome machinery; and (iii) the generation of DNA breaks and subsequent apoptosis...
October 2016: Molecular Cancer Therapeutics
Whitney S Henry, David G Hendrickson, Francisco Beca, Benjamin Glass, Marianne Lindahl-Allen, Lizhi He, Zhe Ji, Kevin Struhl, Andrew H Beck, John L Rinn, Alex Toker
Long non-coding RNAs (lncRNAs) have been implicated in normal cellular homeostasis as well as pathophysiological conditions, including cancer. Here we performed global gene expression profiling of mammary epithelial cells transformed by oncogenic v-Src, and identified a large subset of uncharacterized lncRNAs potentially involved in breast cancer development. Specifically, our analysis revealed a novel lncRNA, LINC00520 that is upregulated upon ectopic expression of oncogenic v-Src, in a manner that is dependent on the transcription factor STAT3...
September 10, 2016: Oncotarget
Ji-Hyun Lee, Xing-Ming Zhao, Ina Yoon, Jin Young Lee, Nam Hoon Kwon, Yin-Ying Wang, Kyung-Min Lee, Min-Joo Lee, Jisun Kim, Hyeong-Gon Moon, Yongho In, Jin-Kao Hao, Kyung-Mii Park, Dong-Young Noh, Wonshik Han, Sunghoon Kim
Despite the explosion in the numbers of cancer genomic studies, metastasis is still the major cause of cancer mortality. In breast cancer, approximately one-fifth of metastatic patients survive 5 years. Therefore, detecting the patients at a high risk of developing distant metastasis at first diagnosis is critical for effective treatment strategy. We hereby present a novel systems biology approach to identify driver mutations escalating the risk of metastasis based on both exome and RNA sequencing of our collected 78 normal-paired breast cancers...
2016: Cell Discovery
Bethany N Hannafon, Yvonne D Trigoso, Cameron L Calloway, Y Daniel Zhao, David H Lum, Alana L Welm, Zhizhuang J Zhao, Kenneth E Blick, William C Dooley, W Q Ding
BACKGROUND: microRNAs are promising candidate breast cancer biomarkers due to their cancer-specific expression profiles. However, efforts to develop circulating breast cancer biomarkers are challenged by the heterogeneity of microRNAs in the blood. To overcome this challenge, we aimed to develop a molecular profile of microRNAs specifically secreted from breast cancer cells. Our first step towards this direction relates to capturing and analyzing the contents of exosomes, which are small secretory vesicles that selectively encapsulate microRNAs indicative of their cell of origin...
2016: Breast Cancer Research: BCR
Martín C Abba, Yi Zhong, Jaeho Lee, Hyunsuk Kil, Yue Lu, Yoko Takata, Melissa S Simper, Sally Gaddis, Jianjun Shen, C Marcelo Aldaz
Controversy always existed on the utility of chemically induced mouse mammary carcinogenesis models as valid equivalents for the study of human breast cancer. Here, we performed whole exome and RNA sequencing on long latency mammary tumors (218 ± 27 days) induced by the carcinogen 7,12-Dimethylbenzathracene (DMBA) and short latency tumors (65 ± 11 days) induced by the progestin Medroxyprogesterone Acetate (MPA) plus DMBA in CD2F1 mice. Long latency tumors displayed a high frequency of Pi3kca and/or Pten mutations detected in 11 of 13 (85%) long latency cases (14/22, 64% overall)...
August 31, 2016: Oncotarget
Jingmei Li, Emma Ivansson, Daniel Klevebring, Nicholas P Tobin, Linda S Lindström, Johanna Holm, Gabriela Prochazka, Camilla Cristando, Juni Palmgren, Sven Törnberg, Keith Humphreys, Johan Hartman, Jan Frisell, Mattias Rantalainen, Johan Lindberg, Per Hall, Jonas Bergh, Henrik Grönberg, Kamila Czene
PURPOSE: Interval breast cancer is of clinical interest as it exhibits an aggressive phenotype and evades detection by screening mammography. A comprehensive picture of somatic changes that drive tumors to become symptomatic in the screening interval can improve understanding of the biology underlying these aggressive tumors. EXPERIMENTAL DESIGN: Initiated in April 2013, Clinical Sequencing of Cancer in Sweden (Clinseq) is a scientific and clinical platform for the genomic profiling of cancer...
September 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Tonje Fiskaa, Erik Knutsen, Marlen Aas Nikolaisen, Tor Erik Jørgensen, Steinar Daae Johansen, Maria Perander, Ole Morten Seternes
Breast cancer is a heterogeneous disease, and different subtypes of breast cancer show distinct cellular morphology, gene expression, metabolism, motility, proliferation, and metastatic potential. Understanding the molecular features responsible for this heterogeneity is important for correct diagnosis and better treatment strategies. Extracellular vesicles (EVs) and their associated molecules have gained much attention as players in intercellular communication, ability to precondition specific organs for metastatic invasion, and for their potential role as circulating cancer biomarkers...
2016: PloS One
Mercedeh Movassagh, Nawaf Alomran, Prakriti Mudvari, Merve Dede, Cem Dede, Kamran Kowsari, Paula Restrepo, Edmund Cauley, Sonali Bahl, Muzi Li, Wesley Waterhouse, Krasimira Tsaneva-Atanasova, Nathan Edwards, Anelia Horvath
We introduce RNA2DNAlign, a computational framework for quantitative assessment of allele counts across paired RNA and DNA sequencing datasets. RNA2DNAlign is based on quantitation of the relative abundance of variant and reference read counts, followed by binomial tests for genotype and allelic status at SNV positions between compatible sequences. RNA2DNAlign detects positions with differential allele distribution, suggesting asymmetries due to regulatory/structural events. Based on the type of asymmetry, RNA2DNAlign outlines positions likely to be implicated in RNA editing, allele-specific expression or loss, somatic mutagenesis or loss-of-heterozygosity (the first three also in a tumor-specific setting)...
August 30, 2016: Nucleic Acids Research
Yanan Li, Weijie Min, Mengmeng Li, Guosheng Han, Dongwei Dai, Lei Zhang, Xin Chen, Xinglai Wang, Yuhui Zhang, Zhijian Yue, Jianmin Liu
Glioblastoma multiforme (GBM) is the most common malignant brain tumor. This study aimed to identify the hub genes and regulatory factors of GBM subgroups by RNA sequencing (RNA-seq) data analysis, in order to explore the possible mechanisms responsbile for the progression of GBM. The dataset RNASeqV2 was downloaded by TCGA-Assembler, containing 169 GBM and 5 normal samples. Gene expression was calculated by the reads per kilobase per million reads measurement, and nor malized with tag count comparison...
October 2016: International Journal of Molecular Medicine
Willemijne A M E Schrijver, Petra van der Groep, Laurien Dc Hoefnagel, Natalie D Ter Hoeve, Ton Peeters, Cathy B Moelans, Paul J van Diest
Distant breast cancer metastases are nowadays routinely biopsied to reassess receptor status and to isolate DNA for sequencing of druggable targets. Bone metastases are the most frequent subgroup. Decalcification procedures may negatively affect antigenicity and DNA quality. We therefore evaluated the effect of several decalcification procedures on receptor status and DNA/RNA quality. In 23 prospectively collected breast tumors, we compared ERα, PR and HER2 status by immunohistochemistry in (non-decalcified) tissue routinely processed for diagnostic purposes and in parallel tissue decalcified in Christensen's buffer with and without microwave, EDTA and Formical-4...
August 26, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Kathleen Oros Klein, Karim Oualkacha, Marie-Hélène Lafond, Sahir Bhatnagar, Patricia N Tonin, Celia M T Greenwood
In a variety of solid cancers, missense mutations in the well-established TP53 tumor suppressor gene may lead to the presence of a partially-functioning protein molecule, whereas mutations affecting the protein encoding reading frame, often referred to as null mutations, result in the absence of p53 protein. Both types of mutations have been observed in the same cancer type. As the resulting tumor biology may be quite different between these two groups, we used RNA-sequencing data from The Cancer Genome Atlas (TCGA) from four different cancers with poor prognosis, namely ovarian, breast, lung and skin cancers, to compare the patterns of coexpression of genes in tumors grouped according to their TP53 missense or null mutation status...
2016: Frontiers in Genetics
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