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https://www.readbyqxmd.com/read/29610475/the-long-tail-of-oncogenic-drivers-in-prostate-cancer
#1
Joshua Armenia, Stephanie A M Wankowicz, David Liu, Jianjiong Gao, Ritika Kundra, Ed Reznik, Walid K Chatila, Debyani Chakravarty, G Celine Han, Ilsa Coleman, Bruce Montgomery, Colin Pritchard, Colm Morrissey, Christopher E Barbieri, Himisha Beltran, Andrea Sboner, Zafeiris Zafeiriou, Susana Miranda, Craig M Bielski, Alexander V Penson, Charlotte Tolonen, Franklin W Huang, Dan Robinson, Yi Mi Wu, Robert Lonigro, Levi A Garraway, Francesca Demichelis, Philip W Kantoff, Mary-Ellen Taplin, Wassim Abida, Barry S Taylor, Howard I Scher, Peter S Nelson, Johann S de Bono, Mark A Rubin, Charles L Sawyers, Arul M Chinnaiyan, Nikolaus Schultz, Eliezer M Van Allen
Comprehensive genomic characterization of prostate cancer has identified recurrent alterations in genes involved in androgen signaling, DNA repair, and PI3K signaling, among others. However, larger and uniform genomic analysis may identify additional recurrently mutated genes at lower frequencies. Here we aggregate and uniformly analyze exome sequencing data from 1,013 prostate cancers. We identify and validate a new class of E26 transformation-specific (ETS)-fusion-negative tumors defined by mutations in epigenetic regulators, as well as alterations in pathways not previously implicated in prostate cancer, such as the spliceosome pathway...
April 2, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29509756/correction-an-autonomous-metabolic-role-for-spen
#2
Kelsey E Hazegh, Travis Nemkov, Angelo D'Alessandro, John D Diller, Jenifer Monks, James L McManaman, Kenneth L Jones, Kirk C Hansen, Tânia Reis
[This corrects the article DOI: 10.1371/journal.pgen.1006859.].
March 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29481902/panel-sequencing-reveals-recurrent-genetic-fas-alterations-in-primary-cutaneous-marginal-zone-lymphoma
#3
Katja Maurus, Silke Appenzeller, Sabine Roth, Jochen Kuper, Simone Rost, Svenja Meierjohann, Panagiota Arampatzi, Matthias Goebeler, Andreas Rosenwald, Eva Geissinger, Marion Wobser
Primary cutaneous marginal zone lymphoma (PCMZL) represents an indolent subtype of Non-Hodgkin lymphomas being clinically characterized by slowly growing tumors of the skin, but a very low propensity for systemic dissemination. Up to now, the underlying genetic basis of PCMZL has not been comprehensively elucidated. With the aim to gain deeper insight into the molecular pathogenesis of PCMZL, we performed hybridization-based panel sequencing of 38 cases of well-characterized PCMZL. In 32 out of 38 cases we identified genetic alterations within 39 selected target genes...
February 23, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29117356/spatio-temporal-genomic-heterogeneity-phylogeny-and-metastatic-evolution-in-salivary-adenoid-cystic-carcinoma
#4
Bin Liu, Yoshitsugu Mitani, Xiayu Rao, Mark Zafereo, Jianjun Zhang, Jianhua Zhang, P Andrew Futreal, Guillermina Lozano, Adel K El-Naggar
Background: Adenoid cystic carcinoma (ACC), an uncommon and indolent salivary gland malignancy, is characterized by varied morphologic and clinical manifestations. Molecular genetic studies of ACC identified certain structural and mutational alterations that may play a driver role in tumor development. The evolution and regional consistency of these events in ACC development progression are uncertain. Methods: To investigate the spatial and temporal clonal landscape of ACC, whole-genome sequencing and variant analyses were performed on 34 regionally sampled primary tumors and their concurrent and metachronous metastatic deposits from eight patients...
October 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28916169/the-large-and-small-spen-family-proteins-stimulate-axon-outgrowth-during-neurosecretory-cell-remodeling-in-drosophila
#5
Tingting Gu, Tao Zhao, Uday Kohli, Randall S Hewes
Split ends (SPEN) is the founding member of a well conserved family of nuclear proteins with critical functions in transcriptional regulation and the post-transcriptional processing and nuclear export of transcripts. In animals, the SPEN proteins fall into two size classes that perform either complementary or antagonistic functions in different cellular contexts. Here, we show that the two Drosophila representatives of this family, SPEN and Spenito (NITO), regulate metamorphic remodeling of the CCAP/bursicon neurosecretory cells...
November 15, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28877752/spen-a-new-player-in-primary-cilia-formation-and-cell-migration-in-breast-cancer
#6
Stéphanie Légaré, Catherine Chabot, Mark Basik
BACKGROUND: The primary cilium is a microtubule-based and nonmotile organelle functioning as a cellular antenna that is involved in the regulation of cell proliferation, differentiation, and migration. In breast cancer cells, the primary cilium is a structure that decreases in incidence with increasing degrees of transformation and may be biologically more important in estrogen receptor (ERα)-negative breast cancer cells. Split ends (SPEN) is an ERα corepressor that we have identified as a tumor suppressor protein in ERα-positive breast cancer cells whose hormone-independent roles in breast cancer have never been explored...
September 6, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28640815/an-autonomous-metabolic-role-for-spen
#7
Kelsey E Hazegh, Travis Nemkov, Angelo D'Alessandro, John D Diller, Jenifer Monks, James L McManaman, Kenneth L Jones, Kirk C Hansen, Tânia Reis
Preventing obesity requires a precise balance between deposition into and mobilization from fat stores, but regulatory mechanisms are incompletely understood. Drosophila Split ends (Spen) is the founding member of a conserved family of RNA-binding proteins involved in transcriptional regulation and frequently mutated in human cancers. We find that manipulating Spen expression alters larval fat levels in a cell-autonomous manner. Spen-depleted larvae had defects in energy liberation from stores, including starvation sensitivity and major changes in the levels of metabolic enzymes and metabolites, particularly those involved in β-oxidation...
June 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28556180/multiple-coil-k-space-interpolation-enhances-resolution-in-single-shot-spatiotemporal-mri
#8
Gilad Liberman, Eddy Solomon, Michael Lustig, Lucio Frydman
PURPOSE: Spatio-temporal encoding (SPEN) experiments can deliver single-scan MR images without folding complications and with robustness to chemical shift and susceptibility artifacts. Further resolution improvements are shown to arise by relying on multiple receivers, to interpolate the sampled data along the low-bandwidth dimension. The ensuing multiple-sensor interpolation is akin to recently introduced SPEN interleaving procedures, albeit without requiring multiple shots. METHODS: By casting SPEN's spatial rasterization in k-space, it becomes evident that local k-data interpolations enabled by multiple receivers are akin to real-space interleaving of SPEN images...
February 2018: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/28197876/enhancing-pancreatic-mass-with-normal-serum-ca19-9-key-mdct-features-to-characterize-pancreatic-neuroendocrine-tumours-from-its-mimics
#9
Liang Zhu, Hua-Dan Xue, Wei Liu, Xuan Wang, Xin Sui, Qin Wang, Daming Zhang, Ping Li, Zheng-Yu Jin
OBJECTIVES: To determine key MDCT features for characterizing pancreatic neuroendocrine tumours (PNET) from their mimics, which manifest as enhancing pancreatic mass with normal serum CA19-9 level. METHODS: This retrospective study had institutional review board approval and informed consent was waived. Preoperative multiphase MDCT of 74 patients with enhancing pancreatic masses and normal serum CA19-9 levels were included. Surgical pathologies were PNET (n = 42), microcystic serous cystadenomas (m-SCN, n = 12) and solid pseudopapillary epithelial neoplasms (SPEN, n = 20)...
May 2017: La Radiologia Medica
https://www.readbyqxmd.com/read/27993827/frantz-s-tumour-solid-pseudopapillary-epithelial-neoplasm-spen
#10
Orapin Tanapanpanit, Samornmas Kanngurn, Krit Pongpirul
No abstract text is available yet for this article.
December 19, 2016: BMJ Case Reports
https://www.readbyqxmd.com/read/27918010/spatially-encoded-2d-and-3d-diffusion-ordered-nmr-spectroscopy
#11
Ludmilla Guduff, Ilya Kuprov, Carine van Heijenoort, Jean-Nicolas Dumez
We show that the acquisition of 3D diffusion-ordered NMR spectroscopy (DOSY) experiments can be accelerated significantly with the use of spatial encoding (SPEN). The SPEN DOSY approach is discussed, analysed with numerical simulation, and illustrated on a mixture of small molecules.
January 5, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/27916658/referenceless-one-dimensional-nyquist-ghost-correction-in-multicoil-single-shot-spatiotemporally-encoded-mri
#12
Ying Chen, Yupeng Liao, Lisha Yuan, Hui Liu, Seong Dae Yun, Nadim Joni Shah, Zhong Chen, Jianhui Zhong
Single-shot spatiotemporally encoded (SPEN) MRI is a novel fast imaging method capable of retaining the time efficiency of single-shot echo planar imaging (EPI) but with distortion artifacts significantly reduced. Akin to EPI, the phase inconsistencies between mismatched even and odd echoes also result in the so-called Nyquist ghosts. However, the characteristic of the SPEN signals provides the possibility of obtaining ghost-free images directly from even and odd echoes respectively, without acquiring additional reference scans...
April 2017: Magnetic Resonance Imaging
https://www.readbyqxmd.com/read/27810749/a-high-throughput-computational-system-to-predict-if-environmental-contaminants-can-bind-to-human-nuclear-receptors
#13
Xiaoxiang Wang, Xiaowei Zhang, Pu Xia, Junjiang Zhang, Yuting Wang, Rui Zhang, John P Giesy, Wei Shi, Hongxia Yu
Some pollutants can bind to nuclear receptors (NRs) and modulate their activities. Predicting interactions of NRs with chemicals is required by various jurisdictions because these molecular initiating events can result in adverse, apical outcomes, such as survival, growth or reproduction. The goal of this study was to develop a high-throughput, computational method to predict potential agonists of NRs, especially for contaminants in the environment or to which people or wildlife are expected to be exposed, including both persistent and pseudo-persistent chemicals...
January 15, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/27718460/sculpting-3d-spatial-selectivity-with-pairs-of-2d-pulses-a-comparison-of-methods
#14
Gil Farkash, Jean-Nicolas Dumez, Lucio Frydman
Enhancing the specificity of the spins' excitation can improve the capabilities of magnetic resonance. Exciting voxels with tailored 3D shapes reduces partial volume effects and enhances contrast, particularly in cases where cubic voxels or other simple geometries do not provide an optimal localization. Spatial excitation profiles of arbitrary shapes can be implemented using so-called multidimensional RF pulses, which are often limited in practice to 2D implementations owing to their sensitivity to field inhomogeneities...
December 2016: Journal of Magnetic Resonance
https://www.readbyqxmd.com/read/27591366/variable-density-sampling-and-non-cartesian-super-resolved-reconstruction-for-spatiotemporally-encoded-single-shot-mri
#15
Lin Chen, Jianpan Huang, Ting Zhang, Jing Li, Congbo Cai, Shuhui Cai
Spatiotemporally encoded (SPEN) single-shot MRI is an emerging ultrafast technique, which is capable of spatially selective acquisition and reduced field-of-view imaging. Compared to uniform sampling, variable density sampling has great potential in reducing aliasing artifacts and improving sampling efficiency. In this study, variable density spiral trajectory and non-Cartesian super-resolved (SR) reconstruction method are developed for SPEN MRI. The gradient waveforms design of spiral trajectory is mathematically described as an optimization problem subjected to the limitations of hardware...
November 2016: Journal of Magnetic Resonance
https://www.readbyqxmd.com/read/27513867/crystal-structure-of-the-spoc-domain-of-the-arabidopsis-flowering-regulator-fpa
#16
Yinglu Zhang, Katarzyna Rataj, Gordon G Simpson, Liang Tong
The Arabidopsis protein FPA controls flowering time by regulating the alternative 3'-end processing of the FLOWERING LOCUS (FLC) antisense RNA. FPA belongs to the split ends (SPEN) family of proteins, which contain N-terminal RNA recognition motifs (RRMs) and a SPEN paralog and ortholog C-terminal (SPOC) domain. The SPOC domain is highly conserved among FPA homologs in plants, but the conservation with the domain in other SPEN proteins is much lower. We have determined the crystal structure of Arabidopsis thaliana FPA SPOC domain at 2...
2016: PloS One
https://www.readbyqxmd.com/read/27494029/whole-exome-sequencing-identifies-tsc1-tsc2-biallelic-loss-as-the-primary-and-sufficient-driver-event-for-renal-angiomyolipoma-development
#17
Krinio Giannikou, Izabela A Malinowska, Trevor J Pugh, Rachel Yan, Yuen-Yi Tseng, Coyin Oh, Jaegil Kim, Magdalena E Tyburczy, Yvonne Chekaluk, Yang Liu, Nicola Alesi, Geraldine A Finlay, Chin-Lee Wu, Sabina Signoretti, Matthew Meyerson, Gad Getz, Jesse S Boehm, Elizabeth P Henske, David J Kwiatkowski
Renal angiomyolipoma is a kidney tumor in the perivascular epithelioid (PEComa) family that is common in patients with Tuberous Sclerosis Complex (TSC) and Lymphangioleiomyomatosis (LAM) but occurs rarely sporadically. Though histologically benign, renal angiomyolipoma can cause life-threatening hemorrhage and kidney failure. Both angiomyolipoma and LAM have mutations in TSC2 or TSC1. However, the frequency and contribution of other somatic events in tumor development is unknown. We performed whole exome sequencing in 32 resected tumor samples (n = 30 angiomyolipoma, n = 2 LAM) from 15 subjects, including three with TSC...
August 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27301072/ultrafast-multi-slice-spatiotemporally-encoded-mri-with-slice-selective-dimension-segmented
#18
Ting Zhang, Lin Chen, Jianpan Huang, Jing Li, Shuhui Cai, Congbo Cai, Zhong Chen
As a recently emerging method, spatiotemporally encoded (SPEN) magnetic resonance imaging (MRI) has a high robustness to field inhomogeneity and chemical shift effect. It has been broadened from single-slice scanning to multi-slice scanning. In this paper, a novel multi-slice SPEN MRI method was proposed. In this method, the slice-selective dimension was segmented to lower the specific absorption rate (SAR) and improve the image quality. This segmented method, dubbed SeSPEN method, was theoretically analyzed and demonstrated with phantom, lemon and in vivo rat brain experiments...
August 2016: Journal of Magnetic Resonance
https://www.readbyqxmd.com/read/27248326/xist-reduction-in-breast-cancer-upregulates-akt-phosphorylation-via-hdac3-mediated-repression-of-phlpp1-expression
#19
Yen-Sung Huang, Che-Chang Chang, Szu-Shuo Lee, Yuh-Shan Jou, Hsiu-Ming Shih
Long noncoding RNAs (lncRNAs) dysregulated in cancer potentially play oncogenic or tumor-suppressive roles. While the X inactivate-specific transcript (Xist) lncRNA is important for X-chromosome inactivation in female cells, very little is known about the role of Xist in human breast cancer in modulating cellular pathway(s). Here, we show that Xist expression is significantly reduced in breast tumor samples and cancer cell lines. Xist knockdown or overexpression resulted in increased or decreased levels, respectively, of AKT phosphorylation and cell viability...
July 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27203401/reducing-sar-requirements-in-multislice-volumetric-single-shot-spatiotemporal-mri-by-two-dimensional-rf-pulses
#20
Gilad Liberman, Lucio Frydman
PURPOSE: Spatiotemporal encoding (SPEN) can deliver single-scan MR images without folding complications and with increased robustness to chemical shift and susceptibility artifacts. Yet, it does so at the expense of relatively high specific absorption rates (SAR) owing to its reliance on frequency-swept pulses. This study describes SPEN implementations aimed at full three-dimensional (3D) multislice imaging, possessing reduced SAR thanks to an implementation based on new 2D radiofrequency (RF) pulses...
May 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
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