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RNA sequencing Breast Cancer

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https://www.readbyqxmd.com/read/28427202/clinical-implications-of-genomic-profiles-in-metastatic-breast-cancer-with-a-focus-on-tp53-and-pik3ca-the-most-frequently-mutated-genes
#1
Ji-Yeon Kim, Eunjin Lee, Kyunghee Park, Woong-Yang Park, Hae Hyun Jung, Jin Seok Ahn, Young-Hyuck Im, Yeon Hee Park
Breast cancer (BC) has been genetically profiled through large-scale genome analyses. However, the role and clinical implications of genetic alterations in metastatic BC (MBC) have not been evaluated. Therefore, we conducted whole-exome sequencing (WES) and RNA-Seq of 37 MBC samples and targeted deep sequencing of another 29 MBCs. We evaluated somatic mutations from WES and targeted sequencing and assessed gene expression and performed pathway analysis from RNA-Seq. In this analysis, PIK3CA was the most commonly mutated gene in estrogen receptor (ER)-positive BC, while in ER-negative BC, TP53 was the most commonly mutated gene (p = 0...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420963/rna-seq-analysis-of-microglia-reveals-time-dependent-activation-of-specific-genetic-programs-following-spinal-cord-injury
#2
Harun N Noristani, Yannick N Gerber, Jean-Charles Sabourin, Marine Le Corre, Nicolas Lonjon, Nadine Mestre-Frances, Hélène E Hirbec, Florence E Perrin
Neurons have inherent competence to regrow following injury, although not spontaneously. Spinal cord injury (SCI) induces a pronounced neuroinflammation driven by resident microglia and infiltrating peripheral macrophages. Microglia are the first reactive glial population after SCI and participate in recruitment of monocyte-derived macrophages to the lesion site. Both positive and negative influence of microglia and macrophages on axonal regeneration had been reported after SCI, raising the issue whether their response depends on time post-lesion or different lesion severity...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28402752/the-microrna-mir-210-is-expressed-by-cancer-cells-but-also-by-the-tumor-microenvironment-in-triple-negative-breast-cancer
#3
Isabelle Bar, Ahmad Merhi, Fadi Abdel-Sater, Abduelhakem Ben Addi, Sara Sollennita, Jean-Luc Canon, Paul Delrée
The triple-negative breast cancer (TNBC) subtype occurs in about 15% of breast cancer and is an aggressive subtype of breast cancer with poor outcome. Furthermore, treatment of patients with TNBC is more challenging due to the heterogeneity of the disease and the absence of well-defined molecular targets. Microribonucleic acid (RNA) represents a new class of biomarkers that are frequently dysregulated in cancer. It has been described that the microRNA miR-210 is highly expressed in TNBC, and its overexpression had been linked to poor prognosis...
April 1, 2017: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/28400268/genetic-evidence-supporting-the-taxonomic-separation-of-the-arabian-and-northwest-african-subspecies-of-the-desert-hedgehog-paraechinus-aethiopicus
#4
Louiza Derouiche, Paul Vercammen, Rachid Bouhadad, Carlos Fernandes
Traditional subspecies call attention to differences between geographic populations with research potential, but their value is often in need of revision. Genetic data can be useful for evaluating the taxonomic validity of historical species and subspecies designations or for identifying morphologically cryptic divergent lineages worthy of further in-depth taxonomic study. The desert hedgehog (Paraechinus aethiopicus) has a wide but fragmented distribution in arid and semi-arid habitats from the northwest to the northeast of Africa and southwestern Asia, and its taxonomy is still unclear...
April 8, 2017: Gene
https://www.readbyqxmd.com/read/28399911/the-role-of-c-myc-rbm38-loop-in-the-growth-suppression-in-breast-cancer
#5
Xiao-Xia Li, Liang Shi, Xu-Jie Zhou, Jing Wu, Tian-Song Xia, Wen-Bin Zhou, Xi Sun, Lei Zhu, Ji-Fu Wei, Qiang Ding
BACKGROUND: RNA-binding protein 38 (RBM38) is a member of the RNA recognition motif (RRM) family of RNA-binding proteins (RBPs). RBM38 often exerts its function by forming regulatory loops with relevant genes. c-Myc is an oncogenic transcription factor that is upregulated in one-third of breast cancers and involved in many cellular processes in this malignancy. In our previous study, RBM38 was identified as a tumor suppressor in breast cancer. In the present study, we investigated the mechanisms underlying the regulation of this tumor suppressor...
April 11, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28398609/potentially-functional-variants-in-lncrnas-are-associated-with-breast-cancer-risk-in-a-chinese-population
#6
Yue Jiang, Fangzhi Du, Fei Chen, Na Qin, Zhu Jiang, Jing Zhou, Tao Jiang, Zhening Pu, Yue Cheng, Jiaping Chen, Juncheng Dai, Hongxia Ma, Guangfu Jin, Zhibin Hu, Hao Yu, Hongbing Shen
Long non-coding RNAs (lncRNAs) participate in the development of breast cancer. Genetic variants in lncRNAs may be involved in their abnormal expressions and associated with cancer risk. In the present study, we performed RNA sequencing on five paired breast cancer tumor and adjacent non-cancerous tissues to obtain differentially expressed lncRNAs. We systematically selected potential regulatory variants of these lncRNAs and investigated the associations between these variants and breast cancer susceptibility in 1,486 breast cancer cases and 1,519 cancer-free controls in a Chinese population...
April 11, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28396358/extracellular-matrix-integrin-signaling-promotes-resistance-to-combined-inhibition-of-her2-and-pi3k-in-her2-breast-cancer
#7
Ariella B Hanker, Monica Valeria Estrada, Giampaolo Bianchini, Preston D Moore, Junfei Zhao, Feixiong Cheng, Luca Gianni, James P Koch, Darren R Tyson, Violeta Sanchez, Brent N Rexer, Melinda Sanders, Zhongming Zhao, Thomas Stricker, Carlos L Arteaga
PIK3CA mutations are associated with resistance to HER2-targeted therapies. We previously showed that HER2+/PIK3CA(H1047R) transgenic mammary tumors are resistant to the HER2 antibodies trastuzumab and pertuzumab but respond to PI3K inhibitor buparlisib (TPB). In this study, we identified mechanisms of resistance to combined inhibition of HER2 and PI3K. TPB-resistant tumors were generated by treating HER2+/PIK3CA(H1047R) mice long-term with the drug combination. RNA-sequencing of TPB-resistant tumors revealed that extracellular matrix (ECM) and cell adhesion genes, including collagen II (Col2a1), were markedly upregulated, accompanied by activation of integrin β1/Src...
April 10, 2017: Cancer Research
https://www.readbyqxmd.com/read/28376728/comparison-of-triple-negative-breast-cancer-molecular-subtyping-using-rna-from-matched-fresh-frozen-versus-formalin-fixed-paraffin-embedded-tissue
#8
Bojana Jovanović, Quanhu Sheng, Robert S Seitz, Kasey D Lawrence, Stephan W Morris, Lance R Thomas, David R Hout, Brock L Schweitzer, Yan Guo, Jennifer A Pietenpol, Brian D Lehmann
BACKGROUND: Triple negative breast cancer (TNBC) is a heterogeneous disease that lacks unifying molecular alterations that can guide therapy decisions. We previously identified distinct molecular subtypes of TNBC (TNBCtype) using gene expression data generated on a microarray platform using frozen tumor specimens. Tumors and cell lines representing the identified subtypes have distinct enrichment in biologically relevant transcripts with differing sensitivity to standard chemotherapies and targeted agents...
April 4, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28376177/progesterone-receptor-isoform-ratio-a-breast-cancer-prognostic-and-predictive-factor-for-antiprogestin-responsiveness
#9
Paola A Rojas, María May, Gonzalo R Sequeira, Andrés Elia, Michelle Alvarez, Paula Martínez, Pedro Gonzalez, Stephen Hewitt, Xiaping He, Charles M Perou, Alfredo Molinolo, Luz Gibbons, Martin C Abba, Hugo Gass, Claudia Lanari
Background: Compelling evidence shows that progestins regulate breast cancer growth. Using preclinical models, we demonstrated that antiprogestins are inhibitory when the level of progesterone receptor isoform A (PR-A) is higher than that of isoform B (PR-B) and that they might stimulate growth when PR-B is predominant. The aims of this study were to investigate ex vivo responses to mifepristone (MFP) in breast carcinomas with different PR isoform ratios and to examine their clinical and molecular characteristics...
July 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28367238/a-comprehensive-ngs-data-analysis-of-differentially-regulated-mirnas-pirnas-lncrnas-and-sn-snornas-in-triple-negative-breast-cancer
#10
Srinivas V Koduru, Amit K Tiwari, Ashley Leberfinger, Sprague W Hazard, Yuka Imamura Kawasawa, Milind Mahajan, Dino J Ravnic
Cancer is the second leading cause of death in the United States and is a major public health concern worldwide. Basic, clinical and epidemiological research is leading to improved cancer detection, prevention, and outcomes. Recent technological advances have allowed unbiased and comprehensive screening of genome-wide gene expression. Small non-coding RNAs (sncRNAs) have been shown to play an important role in biological processes and could serve as a diagnostic, prognostic and therapeutic biomarker for specific diseases...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28346474/the-microrna-205-5p-is-correlated-to-metastatic-potential-of-21t-series-a-breast-cancer-progression-model
#11
L Stankevicins, A Barat, P Dessen, Y Vassetzky, C V de Moura Gallo
MicroRNA is a class of noncoding RNAs able to base pair with complementary messenger RNA sequences, inhibiting their expression. These regulatory molecules play important roles in key cellular processes including cell proliferation, differentiation and response to DNA damage; changes in miRNA expression are a common feature of human cancers. To gain insights into the mechanisms involved in breast cancer progression we conducted a microRNA global expression analysis on a 21T series of cell lines obtained from the same patient during different stages of breast cancer progression...
2017: PloS One
https://www.readbyqxmd.com/read/28344865/identification-of-genetic-determinants-of-breast-cancer-immune-phenotypes-by-integrative-genome-scale-analysis
#12
Wouter Hendrickx, Ines Simeone, Samreen Anjum, Younes Mokrab, François Bertucci, Pascal Finetti, Giuseppe Curigliano, Barbara Seliger, Luigi Cerulo, Sara Tomei, Lucia Gemma Delogu, Cristina Maccalli, Ena Wang, Lance D Miller, Francesco M Marincola, Michele Ceccarelli, Davide Bedognetti
Cancer immunotherapy is revolutionizing the clinical management of several tumors, but has demonstrated limited activity in breast cancer. The development of more effective treatments is hindered by incomplete knowledge of the genetic determinant of immune responsiveness. To fill this gap, we mined copy number alteration, somatic mutation, and expression data from The Cancer Genome Atlas (TCGA). By using RNA-sequencing data from 1,004 breast cancers, we defined distinct immune phenotypes characterized by progressive expression of transcripts previously associated with immune-mediated rejection...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28339459/functional-classification-of-dna-variants-by-hybrid-minigenes-identification-of-30-spliceogenic-variants-of-brca2-exons-17-and-18
#13
Eugenia Fraile-Bethencourt, Beatriz Díez-Gómez, Valeria Velásquez-Zapata, Alberto Acedo, David J Sanz, Eladio A Velasco
Mutation screening of the breast cancer genes BRCA1 and BRCA2 identifies a large fraction of variants of uncertain clinical significance (VUS) whose functional and clinical interpretations pose a challenge for genomic medicine. Likewise, an increasing amount of evidence indicates that genetic variants can have deleterious effects on pre-mRNA splicing. Our goal was to investigate the impact on splicing of a set of reported variants of BRCA2 exons 17 and 18 to assess their role in hereditary breast cancer and to identify critical regulatory elements that may constitute hotspots for spliceogenic variants...
March 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28339031/p53-inducible-long-non-coding-rna-picart1-mediates-cancer-cell-proliferation-and-migration
#14
Yu Cao, Minglin Lin, Yiwen Bu, Hongyan Ling, Yingchun He, Chenfei Huang, Yi Shen, Bob Song, Deliang Cao
Long non-coding RNAs (lncRNAs) function in the development and progression of cancer, but only a small portion of lncRNAs have been characterized to date. A novel lncRNA transcript, 2.53 kb in length, was identified by transcriptome sequencing analysis, and was named p53-inducible cancer-associated RNA transcript 1 (PICART1). PICART1 was found to be upregulated by p53 through a p53-binding site at -1808 to -1783 bp. In breast and colorectal cancer cells and tissues, PICART1 expression was found to be decreased...
March 20, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28337281/c-myc-induced-upregulation-of-lncrna-snhg12-regulates-cell-proliferation-apoptosis-and-migration-in-triple-negative-breast-cancer
#15
Ouchen Wang, Fan Yang, Yehuan Liu, Lin Lv, Ruimin Ma, Chuanzhi Chen, Jiao Wang, Qiufan Tan, Yue Cheng, Erjie Xia, Yizuo Chen, Xiaohua Zhang
Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer, with a significantly higher recurrence and mortality rate. There is an urgent need to uncover the mechanism underlying TNBC and establish therapeutic targets. Long non-coding RNAs (lncRNAs) are involved in a series of biological functions and provide novel insights into the molecular mechanism of cancer. Based on their expression specificity and large number, lncRNAs are likely to serve as the basis for clinical applications in oncology...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28335559/the-optimization-and-characterization-of-an-rna-cleaving-fluorogenic-dnazyme-probe-for-mda-mb-231-cell-detection
#16
Pengcheng Xue, Shengnan He, Yu Mao, Long Qu, Feng Liu, Chunyan Tan, Yuyang Jiang, Ying Tan
Breast cancer is one of the most frequently diagnosed cancers in females worldwide and lacks specific biomarkers for early detection. In a previous study, we obtained a selective RNA-cleaving Fluorogenic DNAzyme (RFD) probe against MDA-MB-231 cells, typical breast cancer cells, through the systematic evolution of ligands by exponential process (SELEX). To improve the performance of this probe for actual application, we carried out a series of optimization experiments on the pH value of a reaction buffer, the type and concentration of cofactor ions, and sequence minimization...
March 21, 2017: Sensors
https://www.readbyqxmd.com/read/28335433/evaluation-and-adaptation-of-a-laboratory-based-cdna-library-preparation-protocol-for-retrospective-sequencing-of-archived-micrornas-from-up-to-35-year-old-clinical-ffpe-specimens
#17
Olivier Loudig, Tao Wang, Kenny Ye, Juan Lin, Yihong Wang, Andrew Ramnauth, Christina Liu, Azadeh Stark, Dhananjay Chitale, Robert Greenlee, Deborah Multerer, Stacey Honda, Yihe Daida, Heather Spencer Feigelson, Andrew Glass, Fergus J Couch, Thomas Rohan, Iddo Z Ben-Dov
Formalin-fixed paraffin-embedded (FFPE) specimens, when used in conjunction with patient clinical data history, represent an invaluable resource for molecular studies of cancer. Even though nucleic acids extracted from archived FFPE tissues are degraded, their molecular analysis has become possible. In this study, we optimized a laboratory-based next-generation sequencing barcoded cDNA library preparation protocol for analysis of small RNAs recovered from archived FFPE tissues. Using matched fresh and FFPE specimens, we evaluated the robustness and reproducibility of our optimized approach, as well as its applicability to archived clinical specimens stored for up to 35 years...
March 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28327926/genomic-characterisation-of-her2-positive-breast-cancer-and-response-to-neoadjuvant-trastuzumab-and-chemotherapy-results-from-the-acosog-z1041-alliance-trial
#18
R Lesurf, O L Griffith, M Griffith, J Hundal, L Trani, M A Watson, R Aft, M J Ellis, D Ota, V J Suman, F Meric-Bernstam, A M Leitch, J C Boughey, G Unzeitig, A U Buzdar, K K Hunt, E R Mardis
Background: HER2 ( ERBB2 ) gene amplification and its corresponding overexpression are present in 15-30% of invasive breast cancers. While HER2-targeted agents are effective treatments, resistance remains a major cause of death. The American College of Surgeons Oncology Group Z1041 trial (NCT00513292) was designed to compare the pathologic complete response (pCR) rate of distinct regimens of neoadjuvant chemotherapy and trastuzumab, but ultimately identified no difference [1]. Patients and methods: In supplement to tissues from 37 Z1041 cases, 11 similarly treated cases were obtained from a single institution study (NCT00353483)...
February 21, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327201/detecting-gene-signature-activation-in-breast-cancer-in-an-absolute-single-patient-manner
#19
E R Paquet, R Lesurf, A Tofigh, V Dumeaux, M T Hallett
BACKGROUND: The ability to reliably identify the state (activated, repressed, or latent) of any molecular process in the tumor of a patient from an individual whole-genome gene expression profile obtained from microarray or RNA sequencing (RNA-seq) promises important clinical utility. Unfortunately, all previous bioinformatics tools are only applicable in large and diverse panels of patients, or are limited to a single specific pathway/process (e.g. proliferation). METHODS: Using a panel of 4510 whole-genome gene expression profiles from 10 different studies we built and selected models predicting the activation status of a compendium of 1733 different biological processes...
March 21, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28303886/molecular-classification-of-lobular-carcinoma-of-the-breast
#20
Denggang Fu, Qi Zuo, Qi Huang, Li Su, Huijun Z Ring, Brian Z Ring
The morphology of breast tumors is complicated and diagnosis can be difficult. We present here a novel diagnostic model which we validate on both array-based and RNA sequencing platforms which reliably distinguishes this tumor type across multiple cohorts. We also examine how this molecular classification predicts sensitivity to common chemotherapeutics in cell-line based assays. A total of 1845 invasive breast cancer cases in six cohorts were collected, split into discovery and validation cohorts, and a classifier was created and compared to pathological diagnosis, grade and survival...
March 17, 2017: Scientific Reports
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