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  1. Article ; Online: Sex differences in SARS-CoV-2 infection rates and the potential link to prostate cancer

    Dimple Chakravarty / Sujit S. Nair / Nada Hammouda / Parita Ratnani / Yasmine Gharib / Vinayak Wagaskar / Nihal Mohamed / Dara Lundon / Zachary Dovey / Natasha Kyprianou / Ashutosh K. Tewari

    Communications Biology, Vol 3, Iss 1, Pp 1-

    2020  Volume 12

    Abstract: Dimple Chakravarty et al. review the rapidly emerging data indicating a higher rate of SARS-CoV-2 ...

    Abstract Dimple Chakravarty et al. review the rapidly emerging data indicating a higher rate of SARS-CoV-2 infection in men. They note that men in the age group most at risk of infection are also at high risk of prostate cancer, and explore the potential links between these diseases and implications for COVID-19 treatment in prostate cancer patients.
    Keywords Biology (General) ; QH301-705.5 ; covid19
    Language English
    Publishing date 2020-07-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: A computational framework discovers new copy number variants with functional importance.

    Samprit Banerjee / Derek Oldridge / Maria Poptsova / Wasay M Hussain / Dimple Chakravarty / Francesca Demichelis

    PLoS ONE, Vol 6, Iss 3, p e

    2011  Volume 17539

    Abstract: Structural variants which cause changes in copy numbers constitute an important component of genomic variability. They account for 0.7% of genomic differences in two individual genomes, of which copy number variants (CNVs) are the largest component. A ... ...

    Abstract Structural variants which cause changes in copy numbers constitute an important component of genomic variability. They account for 0.7% of genomic differences in two individual genomes, of which copy number variants (CNVs) are the largest component. A recent population-based CNV study revealed the need of better characterization of CNVs, especially the small ones (<500 bp).We propose a three step computational framework (Identification of germline Changes in Copy Number or IgC2N) to discover and genotype germline CNVs. First, we detect candidate CNV loci by combining information across multiple samples without imposing restrictions to the number of coverage markers or to the variant size. Secondly, we fine tune the detection of rare variants and infer the putative copy number classes for each locus. Last, for each variant we combine the relative distance between consecutive copy number classes with genetic information in a novel attempt to estimate the reference model bias. This computational approach is applied to genome-wide data from 1250 HapMap individuals. Novel variants were discovered and characterized in terms of size, minor allele frequency, type of polymorphism (gains, losses or both), and mechanism of formation. Using data generated for a subset of individuals by a 42 million marker platform, we validated the majority of the variants with the highest validation rate (66.7%) was for variants of size larger than 1 kb. Finally, we queried transcriptomic data from 129 individuals determined by RNA-sequencing as further validation and to assess the functional role of the new variants. We investigated the possible enrichment for variant's regulatory effect and found that smaller variants (<1 Kb) are more likely to regulate gene transcript than larger variants (p-value = 2.04e-08). Our results support the validity of the computational framework to detect novel variants relevant to disease susceptibility studies and provide evidence of the importance of genetic variants in regulatory network studies.
    Keywords Medicine ; R ; Science ; Q
    Subject code 519
    Language English
    Publishing date 2011-03-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Comparative analysis of 1152 African-American and European-American men with prostate cancer identifies distinct genomic and immunological differences

    Walter Rayford / Alp Tuna Beksac / Jordan Alger / Mohammed Alshalalfa / Mohsen Ahmed / Irtaza Khan / Ugo G. Falagario / Yang Liu / Elai Davicioni / Daniel E. Spratt / Edward M. Schaeffer / Felix Y. Feng / Brandon Mahal / Paul L. Nguyen / Robert B. Den / Mark D. Greenberger / Randy Bradley / Justin M. Watson / Matthew Beamer /
    Lambros Stamatakis / Darrell J. Carmen / Shivanshu Awasthi / Jonathan Hwang / Rachel Weil / Harri Merisaari / Nihal Mohamed / Leslie A. Deane / Dimple Chakravarty / Kamlesh K. Yadav / Kosj Yamoah / Sujit S. Nair / Ashutosh K. Tewari

    Communications Biology, Vol 4, Iss 1, Pp 1-

    2021  Volume 9

    Abstract: Walter Rayford, Alp Tuna Beksac et al. investigated gene expression alterations in African-American and European-American men who underwent radical prostatectomy for prostate cancer. The observed differences include higher expression of inflammation ... ...

    Abstract Walter Rayford, Alp Tuna Beksac et al. investigated gene expression alterations in African-American and European-American men who underwent radical prostatectomy for prostate cancer. The observed differences include higher expression of inflammation genes and lower expression of mismatch repair genes in African-American men.
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2021-06-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Inherited determinants of early recurrent somatic mutations in prostate cancer

    Alessandro Romanel / Sonia Garritano / Blerta Stringa / Mirjam Blattner / Davide Dalfovo / Dimple Chakravarty / David Soong / Kellie A. Cotter / Gianluca Petris / Priyanka Dhingra / Paola Gasperini / Anna Cereseto / Olivier Elemento / Andrea Sboner / Ekta Khurana / Alberto Inga / Mark A. Rubin / Francesca Demichelis

    Nature Communications, Vol 8, Iss 1, Pp 1-

    2017  Volume 10

    Abstract: Prostate cancer is a heterogeneous disease, and many cases show somatic mutations of SPOP. Here, the authors show that a non-coding polymorphic regulatory element at 7p14.3 may predispose to SPOP mutant prostate cancer subclass through a hormone ... ...

    Abstract Prostate cancer is a heterogeneous disease, and many cases show somatic mutations of SPOP. Here, the authors show that a non-coding polymorphic regulatory element at 7p14.3 may predispose to SPOP mutant prostate cancer subclass through a hormone dependent DNA damage response.
    Keywords Science ; Q
    Language English
    Publishing date 2017-06-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Role of PELP1/MNAR signaling in ovarian tumorigenesis.

    Dimple, Chakravarty / Nair, Sujit S / Rajhans, Rajib / Pitcheswara, Perla R / Liu, Jinsong / Balasenthil, Seetharaman / Le, Xiao-Feng / Burow, Matthew E / Auersperg, Nelly / Tekmal, Rajeshwar Rao / Broaddus, Russell R / Vadlamudi, Ratna K

    Cancer research

    2008  Volume 68, Issue 12, Page(s) 4902–4909

    Abstract: Emerging evidence suggests that nuclear receptor (NR) coregulators have potential to act as master genes and their deregulation can promote oncogenesis. Proline-, glutamic acid-, and leucine-rich protein-1 (PELP1/MNAR) is a novel NR coregulator. Its ... ...

    Abstract Emerging evidence suggests that nuclear receptor (NR) coregulators have potential to act as master genes and their deregulation can promote oncogenesis. Proline-, glutamic acid-, and leucine-rich protein-1 (PELP1/MNAR) is a novel NR coregulator. Its expression is deregulated in hormone-driven cancers. However, the role of PELP1/MNAR in ovarian cancer progression remains unknown. Analysis of serial analysis of gene expression data suggested deregulation of PELP1/MNAR expression in ovarian tumors. Western analysis of PELP1/MNAR in normal and serous ovarian tumor tissues showed 3- to 4-fold higher PELP1/MNAR expression in serous tumors compared with normal ovarian tissues. To examine the significance of PELP1/MNAR in ovarian cancer progression, we have generated model cells that overexpress PELP1/MNAR and ovarian cancer cells in which PELP1/MNAR expression is down-regulated by stable expression of PELP1/MNAR-specific shRNA. Down-regulation of PELP1/MNAR in cancerous ovarian model cells (OVCAR3) resulted in reduced proliferation, affected the magnitude of c-Src and protein kinase B (AKT) signaling, and reduced tumorigenic potential of ovarian cancer cells in a nude mouse model. PELP1/MNAR overexpression in nontumorigenic immortalized surface epithelial cells (IOSE cells) promoted constitutive activation of c-Src and AKT signaling pathways and promoted anchorage-independent growth. Immunohistochemical studies using human ovarian cancer tissue arrays (n = 123) showed that PELP1/MNAR is 2- to 3-fold overexpressed in 60% of ovarian tumors, and PELP1/MNAR deregulation occurs in all different types of ovarian cancer. Collectively, these results suggest that PELP1/MNAR signaling plays a role in ovarian cancer cell proliferation and survival, and that its expression is deregulated in ovarian carcinomas.
    MeSH term(s) Adenocarcinoma, Clear Cell/metabolism ; Adenocarcinoma, Clear Cell/pathology ; Adenocarcinoma, Mucinous/metabolism ; Adenocarcinoma, Mucinous/pathology ; Animals ; Carcinoma, Endometrioid/metabolism ; Carcinoma, Endometrioid/pathology ; Cell Adhesion/physiology ; Cell Proliferation ; Co-Repressor Proteins ; Cystadenocarcinoma, Serous/metabolism ; Cystadenocarcinoma, Serous/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunoenzyme Techniques ; Mice ; Mice, Nude ; Ovarian Neoplasms/metabolism ; Ovarian Neoplasms/pathology ; Ovarian Neoplasms/therapy ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; RNA, Small Interfering/pharmacology ; Receptors, Estrogen/metabolism ; Signal Transduction ; Tissue Array Analysis ; Trans-Activators/antagonists & inhibitors ; Trans-Activators/genetics ; Trans-Activators/metabolism ; Transcription Factors ; Tumor Cells, Cultured ; src-Family Kinases/metabolism
    Chemical Substances Co-Repressor Proteins ; PELP1 protein, human ; RNA, Small Interfering ; Receptors, Estrogen ; Trans-Activators ; Transcription Factors ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; src-Family Kinases (EC 2.7.10.2) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
    Language English
    Publishing date 2008-06-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 1432-1
    ISSN 1538-7445 ; 0008-5472
    ISSN (online) 1538-7445
    ISSN 0008-5472
    DOI 10.1158/0008-5472.CAN-07-5698
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Integrative Annotation of Variants from 1092 Humans: Application to Cancer Genomics

    Khurana, Ekta / Alexej Abyzov / Andrea Sboner / Arif Harmanci / Chris Tyler-Smith / Cristina Sisu / Daniel Challis / Daniel G. MacArthur / Declan Clarke / Dimple Chakravarty / Donna Muzny / Emmanouil T. Dermitzakis / Erik Garrison / Fiona Cunningham / Fuli Yu / Gabor Marth / Graham R. S. Ritchie / Haiyuan Yu / Hyun Min Kang /
    Javier Herrero / Jeffrey A. Rosenfeld / Jieming Chen / Jishnu Das / Kasper Lage / Kathryn Beal / Laura Clarke / Lucas Lochovsky / Mark A. Rubin / Mark Gerstein / Michael Wilson / Naoki Kitabayashi / Paul Flicek / Richard Gibbs / Robert Fragoza / Steven M. Lipkin / Suganthi Balasubramanian / Tune H. Pers / Tuuli Lappalainen / Uday S. Evani / Vaja Liluashvili / Vincenza Colonna / Xiaomu Wei / Xinmeng Jasmine Mu / Yali Xue / Yao Fu / Yong Kong / Yuan Chen / Zeynep H. Gümüş

    Science. 2013 Oct. 4, v. 342, no. 6154

    2013  

    Abstract: Identifying Important Identifiers Each of us has millions of sequence variations in our genomes. Signatures of purifying or negative selection should help identify which of those variations is functionally important. Khurana et al. (1235587) used ... ...

    Abstract Identifying Important Identifiers Each of us has millions of sequence variations in our genomes. Signatures of purifying or negative selection should help identify which of those variations is functionally important. Khurana et al. (1235587) used sequence polymorphisms from 1092 humans across 14 populations to identify patterns of selection, especially in noncoding regulatory regions. Noncoding regions under very strong negative selection included binding sites of some chromatin and general transcription factors (TFs) and core motifs of some important TF families. Positive selection in TF binding sites tended to occur in network hub promoters. Many recurrent somatic cancer variants occurred in noncoding regulatory regions and thus might indicate mutations that drive cancer.
    Keywords binding sites ; chromatin ; genome ; genomics ; humans ; mutation ; neoplasms ; transcription (genetics) ; transcription factors
    Language English
    Dates of publication 2013-1004
    Size p. 1235587.
    Publishing place American Association for the Advancement of Science
    Document type Article
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.1235587
    Database NAL-Catalogue (AGRICOLA)

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