DOCSLIB.ORG

Molecular Features of the Basal-Like Breast Cancer Subtype Based on BRCA1 Mutation Status

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Molecular Features of the Basal-Like Breast Cancer Subtype Based on BRCA1 Mutation Status Molecular features of the basal-like breast cancer subtype based on BRCA1 mutation status Aleix Prat, Cristina Cruz, Katherine A. Hoadley, Orland Díez, Charles M. Perou & Judith Balmaña Breast Cancer Research and Treatment ISSN 0167-6806 Breast Cancer Res Treat DOI 10.1007/s10549-014-3056-x 1 23 Your article is published under the Creative Commons Attribution Non-Commercial license which allows users to read, copy, distribute and make derivative works for noncommercial purposes from the material, as long as the author of the original work is cited. All commercial rights are exclusively held by Springer Science + Business Media. You may self-archive this article on your own website, an institutional repository or funder’s repository and make it publicly available immediately. 1 23 Breast Cancer Res Treat DOI 10.1007/s10549-014-3056-x BRIEF REPORT Molecular features of the basal-like breast cancer subtype based on BRCA1 mutation status Aleix Prat • Cristina Cruz • Katherine A. Hoadley • Orland Dı´ez • Charles M. Perou • Judith Balman˜a Received: 23 January 2014 / Accepted: 5 July 2014 Ó The Author(s) 2014. This article is published with open access at Springerlink.com Abstract BRCA1-mutated breast cancer is associated miRNA expression, and DNA methylation variation, with basal-like disease; however, it is currently unclear if according to BRCA1 status (either germinal or somatic). the presence of a BRCA1 mutation depicts a different entity However, there were significant differences according to within this subgroup. In this study, we compared the average number of mutations and DNA copy-number molecular features among basal-like tumors with and aberrations, and four amplified regions (2q32.2, 3q29, without BRCA1 mutations. Fourteen patients with BRCA1- 6p22.3, and 22q12.2), which are characteristic in high- mutated (nine germline and five somatic) tumors and basal- grade serous ovarian carcinomas, were observed in both like disease, and 79 patients with BRCA1 non-mutated germline and somatic BRCA1-mutated breast tumors. tumors and basal-like disease, were identified from the These results suggest that minor, but potentially relevant, cancer genome atlas dataset. The following molecular data baseline molecular features exist among basal-like tumors types were evaluated: global gene expression, selected according to BRCA1 status. Additional studies are needed protein and phospho-protein expression, global miRNA to better clarify if BRCA1 genetic status is an independent expression, global DNA methylation, total number of prognostic feature, and more importantly, if BRCA1 somatic mutations, TP53 and PIK3CA somatic mutations, mutation status is a predictive biomarker of benefit from and global DNA copy-number aberrations. For intrinsic DNA-damaging agents among basal-like disease. subtype identification, we used the PAM50 subtype pre- dictor. Within the basal-like disease, we observed minor Keywords Basal-like Á BRCA1 Á Intrinsic subtype Á molecular differences in terms of gene, protein, and Breast cancer Abbreviations Aleix Prat and Cristina Cruz have contributed equally to this work. TN Triple-negative BRCA1 Breast cancer 1 early onset Electronic supplementary material The online version of this article (doi:10.1007/s10549-014-3056-x) contains supplementary material, which is available to authorized users. A. Prat (&) K. A. Hoadley Á C. M. Perou Translational Genomics Group, Vall d´Hebron Institute of Lineberger Comprehensive Cancer Center, University of North Oncology (VHIO), Pg Vall d´Hebron, 119-129, 08035 Barcelona, Carolina at Chapel Hill, Chapel Hill, NC 27514, USA Spain e-mail: [email protected] e-mail: [email protected] C. M. Perou e-mail: [email protected] C. Cruz Á J. Balman˜a High Risk and Cancer Prevention Group, Vall d´Hebron Institute O. Dı´ez of Oncology (VHIO), 08035 Barcelona, Spain Oncogenetics Group, Hospital Universitari de la Vall d´Hebron, e-mail: [email protected] Vall d´Hebron Institute of Oncology (VHIO), 08035 Barcelona, J. Balman˜a Spain e-mail: [email protected] e-mail: [email protected] 123 Breast Cancer Res Treat ID4 Inhibitor of DNA binding 4, dominant negative methylation variation: ‘‘BRCA.methylation.27 k.450 k.txt.’’ helix-loop-helix protein For microarray DNA copy-number aberration data: PIK3CA Phosphatidylinositol-4, 5-bisphosphate ‘‘brca_scna_all_thresholded.by_genes.txt.’’ For intrinsic 3-kinase, catalytic subunit alpha subtype identification, we used the PAM50 subtype calls as provided in the TCGA portal. Independent dataset Introduction We evaluated an independent and publicly available microarray-based gene expression dataset (GSE40115) that Studies based on gene expression data have identified and includes breast tumors from 32 patients with basal-like characterized four main intrinsic subtypes of breast cancer disease (20 with BRCA1 germline mutations and 12 with (luminal A, luminal B, HER2-enriched, and basal-like) [1, sporadic tumors [i.e. unknown BRCA1 status]). The file 2]. Among them, the basal-like subtype is associated with ‘‘GSE40115-GPL15931_series_matrix.txt’’ with the nor- young age, BRCA1 germline and somatic mutations [1, 3, malized log2 ratios (Cy5 sample/Cy3 control) of probes 4] and an overall poor prognosis despite that a subgroup of was used. Probes mapping to the same gene (Entrez ID as patients with these tumors has an excellent outcome when defined by the manufacturer) were averaged to generate treated with chemotherapy [5]. In the clinical setting, basal- independent expression estimates. like tumors are usually identified by the lack of expression of hormone receptors by immunohistochemistry (IHC) and Seven-TN subtype classification lack of overexpression of HER2 by IHC and/or FISH (the so called triple-negative [TN] status) [1, 2, 6]. Although the To identify the 7-TN subtypes described by Lehmann et al. TN definition enriches for basal-like disease, considerable [16], (i.e., basal one, basal two, immunomodulatory, discordance exists [2, 6]. luminal androgen receptor, mesenchymal, mesenchymal BRCA1 mutations and other associated molecular traits stem cell, and unstable), we submitted the raw gene might confer sensitivity to specific therapeutic agents [7– expression data of each individual dataset of basal-like 10]. Nevertheless, it is unclear how different, from a bio- disease to the TNBC type online predictor (http://cbc.mc. logical perspective, BRCA1-mutated basal-like tumors are vanderbilt.edu/tnbc/) [17]. from BRCA1 non-mutated basal-like tumors, and whether BRCA1 mutation is an independent prognostic and/or pre- Statistical analysis dictive biomarker when the intrinsic subtype is taken into account [11–15]. This line of thought directed us to for- All multiple-testing comparisons were done using an unpaired mulate the question of how much the biology of basal-like two-class significance analysis of microarrays (SAM, http:// tumors with BRCA1 mutations differs from the biology of www-stat.stanford.edu/*tibs/SAM/). The mutation rates of basal-like tumors without BRCA1 mutations. To address TP53 and PIK3CA genes between two groups, the 7-TN this question, we interrogated The Cancer Genome Atlas subtype distribution between BRCA1-mutated and non- (TCGA) breast cancer project which provides various types mutated basal-like tumors, and the amplification rates of ID4 of molecular data coming from DNA, RNAs, and proteins between two groups, were compared using the Chi square and [1]. Fisher’s exact tests. The total number of somatic mutations between two groups was compared using a Student’s t test. All statistical computations were performed in R v.2.15.1 (http:// Methods cran.r-project.org). The Cancer Genome Atlas dataset Results and discussion In this study, we evaluated TCGA breast cancer dataset and all data were obtained from the TCGA breast cancer online portal From TCGA breast cancer dataset, we identified 12 tumor (https://tcga-data.nci.nih.gov/docs/publications/brca_2012/). samples with BRCA1 germline mutations (all classified as The following files were used. For microarray gene expres- deleterious), seven tumor samples with somatic BRCA1 sion data: ‘‘BRCA.exp.547.med.txt.’’ For reverse-phase mutations, and one tumor sample with both BRCA1 protein array (RPPA) expression data: ‘‘rppaData- germline and somatic mutations (Supplemental Material). 403Samp-171Ab-Trimmed.txt.’’ For sequencing miRNA As expected, 70 % of BRCA1 mutated tumors where of the expression: ‘‘BRCA.780.mimat.txt.’’ For microarray DNA basal-like intrinsic subtype (nine germline and five 123 Breast Cancer Res Treat Fig. 1 Intrinsic profile of BRCA1-mutated breast tumors. Hierarchical clustering of 509 breast samples of the cancer genome atlas (TCGA) project using the *1,900 intrinsic gene list [30]. PAM50 intrinsic subtype calls [30] and BRCA1 mutation status is shown below the array tree Table 1 Significant molecular Total biomarkers evaluated Type of Comparison Significant Percentage differences between basal-like evaluation (more expressed biomarkers of altered BRCA1-mutated tumors or amplified) identified biomarkers (%) (n = 14) and basal-like BRCA1 (FDR = 0%) non-mutated tumors (n = 79) 17,786 (unique genes) Expression BRCA1MUT 0 0 BRCA1WT 0 171 (unique proteins or Expression BRCA1MUT 0 0.6 phospho-proteins by BRCA1WT 1 RPPA) 1,222 (mature/star miRNA Expression BRCA1MUT 3 0.2 strands) BRCA1WT 0 530 (unique genes) Methylation BRCA1MUT 0 1.1 RPPA reverse-phase protein BRCA1WT 6 arrays, FDR false discovery rate 19,613 (unique genes) DNA BRCA1MUT 250 1.3 BRCA1WT BRCA1 wild-type, amplification BRCA1WT 0 BRCA1MUT BRCA1 mutated somatic), but luminal A (two germline, one germline/ somatic, and one somatic), luminal B (one germline), and HER2-enriched (one somatic) tumors were also identified (Fig. 1). Similarly, 66.7 % of BRCA1 mutated tumors were TN. Within basal-like disease, we observed minor molecular differences (0–1.1 %) in terms of gene expression, protein expression, miRNA expression, and DNA methylation variation according to BRCA1 status (Table 1 and Sup- plemental Material). Indeed, no genes among 17,876 genes were found differentially expressed between basal-like BRCA1-mutated tumors versus basal-like BRCA1 non- mutated tumors (Table 1), including the BRCA1 mRNA transcript (Fig.
Load more

Recommended publications
  • SMARCB1/INI1 Genetic Inactivation Is Responsible for Tumorigenic Properties of Epithelioid Sarcoma Cell Line VAESBJ
    Published OnlineFirst April 10, 2013; DOI: 10.1158/1535-7163.MCT-13-0005 Molecular Cancer Cancer Therapeutics Insights Therapeutics SMARCB1/INI1 Genetic Inactivation Is Responsible for Tumorigenic Properties of Epithelioid Sarcoma Cell Line VAESBJ Monica Brenca1, Sabrina Rossi3, Erica Lorenzetto1, Elena Piccinin1, Sara Piccinin1, Francesca Maria Rossi2, Alberto Giuliano1, Angelo Paolo Dei Tos3, Roberta Maestro1, and Piergiorgio Modena1 Abstract Epithelioid sarcoma is a rare soft tissue neoplasm that usually arises in the distal extremities of young adults. Epithelioid sarcoma presents a high rate of recurrences and metastases and frequently poses diagnostic dilemmas. We previously reported loss of tumor suppressor SMARCB1 protein expression and SMARCB1 gene deletion in the majority of epithelioid sarcoma cases. Unfortunately, no appropriate preclinical models of such genetic alteration in epithelioid sarcoma are available. In the present report, we identified lack of SMARCB1 protein due to a homozygous deletion of exon 1 and upstream regulatory region in epithelioid sarcoma cell line VAESBJ. Restoration of SMARCB1 expression significantly affected VAESBJ cell proliferation, anchorage-independent growth, and cell migration properties, thus supporting the causative role of SMARCB1 loss in epithelioid sarcoma pathogenesis. We investigated the translational relevance of this genetic back- ground in epithelioid sarcoma and showed that SMARCB1 ectopic expression significantly augmented VAESBJ sensitivity to gamma irradiation and acted synergistically with flavopiridol treatment. In VAESBJ, both activated ERBB1/EGFR and HGFR/MET impinged on AKT and ERK phosphorylation. We showed a synergistic effect of combined inhibition of these 2 receptor tyrosine kinases using selective small-molecule inhibitors on cell proliferation. These observations provide definitive support to the role of SMARCB1 inactivation in the pathogenesis of epithelioid sarcoma and disclose novel clues to therapeutic approaches tailored to SMARCB1-negative epithelioid sarcoma.
    [Show full text]
  • Integrase Interactor 1 (INI-1) Deficient Renal Cell Carcinoma
    Open Access Case Report DOI: 10.7759/cureus.13082 Integrase Interactor 1 (INI-1) Deficient Renal Cell Carcinoma Manpreet Singh 1 , Harkirat Singh 1 , Benjamin Hambro 1 , Jasleen Kaur 1 , Ravi Rao 2 1. Internal Medicine, St Agnes Medical Center, Fresno, USA 2. Hematology and Oncology, St Agnes Medical Center, Fresno, USA Corresponding author: Manpreet Singh, [email protected] Abstract Members of the SWItch/sucrose nonfermentable (SWI-SNF) family, including SWI/SNF related, matrix- associated, actin-dependent regulator of chromatin, subfamily A, member 4 (SMARCA4), SWI/SNF related, matrix‐associated, actin‐dependent regulator of chromatin, subfamily B member 1 (SMARCB1)/integrase interactor 1 (INI-1) are known tumor suppressor genes. Interactions between SMARCB1/INI-1 and key protein components in various cellular pathways are related to tumor progression and proliferation. SMARCB1/INI-1 protein was undetectable in rhabdoid tumor cells, whereas non-tumorous cells express the SMARCB1/INI-1 genes. Germline and sporadic mutations of several genes encoding for proteins in this complex are known to cause a spectrum of cancers, usually with sarcomatoid features which include a very aggressive renal medullary carcinoma. We report a case of a 29-year-old male who presented with SMARCA4 deficient renal tumor with a very aggressive clinical behavior which ultimately led to his death. Categories: Nephrology, Oncology Keywords: renal medullary carcinoma, ini-1, renal cell carcinoma, swi/snf, smarcb1, integrase interactor 1 Introduction Renal medullary carcinoma is a rare and very aggressive malignancy affecting young adults with rare cases in patients with sickle cell disease or trait [1]. The tumor arises predominantly in the renal medulla and exhibits a variety of growth patterns including reticular, solid, tubular, trabecular, cribriform, sarcomatoid, and micropapillary [1].
    [Show full text]
  • SEC23IP (NM 007190) Human Recombinant Protein – TP309056
    OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for TP309056 SEC23IP (NM_007190) Human Recombinant Protein Product data: Product Type: Recombinant Proteins Description: Recombinant protein of human SEC23 interacting protein (SEC23IP) Species: Human Expression Host: HEK293T Tag: C-Myc/DDK Predicted MW: 110.9 kDa Concentration: >50 ug/mL as determined by microplate BCA method Purity: > 80% as determined by SDS-PAGE and Coomassie blue staining Buffer: 25 mM Tris.HCl, pH 7.3, 100 mM glycine, 10% glycerol Preparation: Recombinant protein was captured through anti-DDK affinity column followed by conventional chromatography steps. Storage: Store at -80°C. Stability: Stable for 12 months from the date of receipt of the product under proper storage and handling conditions. Avoid repeated freeze-thaw cycles. RefSeq: NP_009121 Locus ID: 11196 UniProt ID: Q9Y6Y8 RefSeq Size: 7306 Cytogenetics: 10q26.11-q26.12 RefSeq ORF: 3000 Synonyms: iPLA1beta; MSTP053; P125; P125A Summary: This gene encodes a member of the phosphatidic acid preferring-phospholipase A1 family. The encoded protein is localized to endoplasmic reticulum exit sites and plays a critical role in ER-Golgi transport as part of the multimeric coat protein II complex. An orthologous gene in frogs is required for normal neural crest cell development, suggesting that this gene may play a role in Waardenburg syndrome neural crest defects. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Feb 2011] This product is to be used for laboratory only.
    [Show full text]
  • Loss of Integrase Interactor 1 (INI1) Expression in a Subset of Differentiated Thyroid Cancer
    diagnostics Article Loss of Integrase Interactor 1 (INI1) Expression in a Subset of Differentiated Thyroid Cancer Kung-Chen Ho 1, Jie-Jen Lee 1, Chi-Hsin Lin 2,3, Ching-Hsiang Leung 4 and Shih-Ping Cheng 1,5,* 1 Department of Surgery, MacKay Memorial Hospital and Mackay Medical College, Taipei 104215, Taiwan; [email protected] (K.-C.H.); [email protected] (J.-J.L.) 2 Department of Medical Research, MacKay Memorial Hospital, Taipei 104215, Taiwan; [email protected] 3 Department of Bioscience Technology, Chung Yuan Christian University, Taoyuan City 320314, Taiwan 4 Division of Endocrinology and Metabolism, Department of Internal Medicine, MacKay Memorial Hospital and Mackay Medical College, Taipei 104215, Taiwan; [email protected] 5 Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110301, Taiwan * Correspondence: [email protected]; Tel.: +886-2-2543-3535 Received: 19 April 2020; Accepted: 2 May 2020; Published: 5 May 2020 Abstract: Alterations in the switching defective/sucrose non-fermenting (SWI/SNF) chromatin-remodeling complex are enriched in advanced thyroid cancer. Integrase interactor 1 (INI1), encoded by the SMARCB1 gene on the long arm of chromosome 22, is one of the core subunits of the SWI/SNF complex. INI1 immunohistochemistry is frequently used for the diagnosis of malignant rhabdoid neoplasms. In the present study, we found normal and benign thyroid tissues generally had diffusely intense nuclear immunostaining. Loss of INI1 immunohistochemical expression was observed in 8% of papillary thyroid cancer and 30% of follicular thyroid cancer. Furthermore, loss of INI1 expression was associated with extrathyroidal extension (p < 0.001) and lymph node metastasis (p = 0.038).
    [Show full text]
  • Renal Medullary Carcinomas Depend Upon SMARCB1 Loss And
    RESEARCH ARTICLE Renal medullary carcinomas depend upon SMARCB1 loss and are sensitive to proteasome inhibition Andrew L Hong1,2,3, Yuen-Yi Tseng3, Jeremiah A Wala3, Won-Jun Kim2, Bryan D Kynnap2, Mihir B Doshi3, Guillaume Kugener3, Gabriel J Sandoval2,3, Thomas P Howard2, Ji Li2, Xiaoping Yang3, Michelle Tillgren2, Mahmhoud Ghandi3, Abeer Sayeed3, Rebecca Deasy3, Abigail Ward1,2, Brian McSteen4, Katherine M Labella2, Paula Keskula3, Adam Tracy3, Cora Connor5, Catherine M Clinton1,2, Alanna J Church1, Brian D Crompton1,2,3, Katherine A Janeway1,2, Barbara Van Hare4, David Sandak4, Ole Gjoerup2, Pratiti Bandopadhayay1,2,3, Paul A Clemons3, Stuart L Schreiber3, David E Root3, Prafulla C Gokhale2, Susan N Chi1,2, Elizabeth A Mullen1,2, Charles WM Roberts6, Cigall Kadoch2,3, Rameen Beroukhim2,3,7, Keith L Ligon2,3,7, Jesse S Boehm3, William C Hahn2,3,7* 1Boston Children’s Hospital, Boston, United States; 2Dana-Farber Cancer Institute, Boston, United States; 3Broad Institute of Harvard and MIT, Cambridge, United States; 4Rare Cancer Research Foundation, Durham, United States; 5RMC Support, North Charleston, United States; 6St. Jude Children’s Research Hospital, Memphis, United States; 7Brigham and Women’s Hospital, Boston, United States Abstract Renal medullary carcinoma (RMC) is a rare and deadly kidney cancer in patients of African descent with sickle cell trait. We have developed faithful patient-derived RMC models and using whole-genome sequencing, we identified loss-of-function intronic fusion events in one SMARCB1 allele with concurrent loss of the other allele. Biochemical and functional characterization of these models revealed that RMC requires the loss of SMARCB1 for survival.
    [Show full text]
  • Genetic Variant in 3' Untranslated Region of the Mouse Pycard Gene
    bioRxiv preprint doi: https://doi.org/10.1101/2021.03.26.437184; this version posted March 26, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. 1 2 3 Title: 4 Genetic Variant in 3’ Untranslated Region of the Mouse Pycard Gene Regulates Inflammasome 5 Activity 6 Running Title: 7 3’UTR SNP in Pycard regulates inflammasome activity 8 Authors: 9 Brian Ritchey1*, Qimin Hai1*, Juying Han1, John Barnard2, Jonathan D. Smith1,3 10 1Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, 11 Cleveland, OH 44195 12 2Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 13 44195 14 3Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western 15 Reserve University, Cleveland, OH 44195 16 *, These authors contributed equally to this study. 17 Address correspondence to Jonathan D. Smith: email [email protected]; ORCID ID 0000-0002-0415-386X; 18 mailing address: Cleveland Clinic, Box NC-10, 9500 Euclid Avenue, Cleveland, OH 44195, USA. 19 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.03.26.437184; this version posted March 26, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. 20 Abstract 21 Quantitative trait locus mapping for interleukin-1 release after inflammasome priming and activation 22 was performed on bone marrow-derived macrophages (BMDM) from an AKRxDBA/2 strain intercross.
    [Show full text]
  • TITLE PAGE Oxidative Stress and Response to Thymidylate Synthase
    Downloaded from molpharm.aspetjournals.org at ASPET Journals on October 2, 2021 -Targeted -Targeted 1 , University of of , University SC K.W.B., South Columbia, (U.O., Carolina, This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted.
    [Show full text]
  • Identification of Potential Key Genes and Pathway Linked with Sporadic Creutzfeldt-Jakob Disease Based on Integrated Bioinformatics Analyses
    medRxiv preprint doi: https://doi.org/10.1101/2020.12.21.20248688; this version posted December 24, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Identification of potential key genes and pathway linked with sporadic Creutzfeldt-Jakob disease based on integrated bioinformatics analyses Basavaraj Vastrad1, Chanabasayya Vastrad*2 , Iranna Kotturshetti 1. Department of Biochemistry, Basaveshwar College of Pharmacy, Gadag, Karnataka 582103, India. 2. Biostatistics and Bioinformatics, Chanabasava Nilaya, Bharthinagar, Dharwad 580001, Karanataka, India. 3. Department of Ayurveda, Rajiv Gandhi Education Society`s Ayurvedic Medical College, Ron, Karnataka 562209, India. * Chanabasayya Vastrad [email protected] Ph: +919480073398 Chanabasava Nilaya, Bharthinagar, Dharwad 580001 , Karanataka, India NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2020.12.21.20248688; this version posted December 24, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Abstract Sporadic Creutzfeldt-Jakob disease (sCJD) is neurodegenerative disease also called prion disease linked with poor prognosis. The aim of the current study was to illuminate the underlying molecular mechanisms of sCJD. The mRNA microarray dataset GSE124571 was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened.
    [Show full text]
  • Curcumin Alters Gene Expression-Associated DNA Damage, Cell Cycle, Cell Survival and Cell Migration and Invasion in NCI-H460 Human Lung Cancer Cells in Vitro
    ONCOLOGY REPORTS 34: 1853-1874, 2015 Curcumin alters gene expression-associated DNA damage, cell cycle, cell survival and cell migration and invasion in NCI-H460 human lung cancer cells in vitro I-TSANG CHIANG1,2, WEI-SHU WANG3, HSIN-CHUNG LIU4, SU-TSO YANG5, NOU-YING TANG6 and JING-GUNG CHUNG4,7 1Department of Radiation Oncology, National Yang‑Ming University Hospital, Yilan 260; 2Department of Radiological Technology, Central Taiwan University of Science and Technology, Taichung 40601; 3Department of Internal Medicine, National Yang‑Ming University Hospital, Yilan 260; 4Department of Biological Science and Technology, China Medical University, Taichung 404; 5Department of Radiology, China Medical University Hospital, Taichung 404; 6Graduate Institute of Chinese Medicine, China Medical University, Taichung 404; 7Department of Biotechnology, Asia University, Taichung 404, Taiwan, R.O.C. Received March 31, 2015; Accepted June 26, 2015 DOI: 10.3892/or.2015.4159 Abstract. Lung cancer is the most common cause of cancer CARD6, ID1 and ID2 genes, associated with cell survival and mortality and new cases are on the increase worldwide. the BRMS1L, associated with cell migration and invasion. However, the treatment of lung cancer remains unsatisfactory. Additionally, 59 downregulated genes exhibited a >4-fold Curcumin has been shown to induce cell death in many human change, including the DDIT3 gene, associated with DNA cancer cells, including human lung cancer cells. However, the damage; while 97 genes had a >3- to 4-fold change including the effects of curcumin on genetic mechanisms associated with DDIT4 gene, associated with DNA damage; the CCPG1 gene, these actions remain unclear. Curcumin (2 µM) was added associated with cell cycle and 321 genes with a >2- to 3-fold to NCI-H460 human lung cancer cells and the cells were including the GADD45A and CGREF1 genes, associated with incubated for 24 h.
    [Show full text]
  • SEC23IP (NM 007190) Human Tagged ORF Clone – RG209056
    OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for RG209056 SEC23IP (NM_007190) Human Tagged ORF Clone Product data: Product Type: Expression Plasmids Product Name: SEC23IP (NM_007190) Human Tagged ORF Clone Tag: TurboGFP Symbol: SEC23IP Synonyms: iPLA1beta; MSTP053; P125; P125A Vector: pCMV6-AC-GFP (PS100010) E. coli Selection: Ampicillin (100 ug/mL) Cell Selection: Neomycin This product is to be used for laboratory only. Not for diagnostic or therapeutic use. View online » ©2021 OriGene Technologies, Inc., 9620 Medical Center Drive, Ste 200, Rockville, MD 20850, US 1 / 4 SEC23IP (NM_007190) Human Tagged ORF Clone – RG209056 ORF Nucleotide >RG209056 representing NM_007190 Sequence: Red=Cloning site Blue=ORF Green=Tags(s) TTTTGTAATACGACTCACTATAGGGCGGCCGGGAATTCGTCGACTGGATCCGGTACCGAGGAGATCTGCC GCCGCGATCGCC ATGGCCGAGAGAAAACCTAACGGTGGCAGCGGCGGCGCCTCCACTTCCTCATCGGGCACTAACTTACTTT TCTCCTCCTCGGCCACGGAGTTCAGCTTCAATGTGCCCTTCATCCCAGTCACCCAGGCCTCCGCTTCTCC GGCCTCCCTGCTCTTACCGGGAGAGGATTCCACAGATGTTGGTGAGGAGGACAGCTTCCTTGGTCAGACT TCTATTCACACATCTGCCCCACAGACATTTAGTTACTTCTCTCAGGTATCAAGCAGCAGTGATCCTTTTG GGAATATTGGACAGTCACCATTAACAACTGCAGCAACCTCAGTTGGACAATCAGGATTCCCCAAGCCCCT GACTGCTCTCCCTTTTACAACTGGATCCCAAGATGTCTCGAATGCATTTTCACCATCCATTTCGAAGGCT CAACCTGGTGCTCCACCTTCCTCACTGATGGGAATAAATTCTTATCTGCCTTCTCAGCCAAGTAGTCTCC CTCCTTCATATTTTGGGAACCAACCCCAAGGAATTCCCCAACCAGGATACAATCCATATCGCCATACCCC TGGCAGCAGCAGGGCTAATCCTTACATTGCACCACCCCAGCTGCAGCAGTGCCAAACACCAGGCCCTCCT
    [Show full text]
  • The Genetics of Bipolar Disorder
    Molecular Psychiatry (2008) 13, 742–771 & 2008 Nature Publishing Group All rights reserved 1359-4184/08 $30.00 www.nature.com/mp FEATURE REVIEW The genetics of bipolar disorder: genome ‘hot regions,’ genes, new potential candidates and future directions A Serretti and L Mandelli Institute of Psychiatry, University of Bologna, Bologna, Italy Bipolar disorder (BP) is a complex disorder caused by a number of liability genes interacting with the environment. In recent years, a large number of linkage and association studies have been conducted producing an extremely large number of findings often not replicated or partially replicated. Further, results from linkage and association studies are not always easily comparable. Unfortunately, at present a comprehensive coverage of available evidence is still lacking. In the present paper, we summarized results obtained from both linkage and association studies in BP. Further, we indicated new potential interesting genes, located in genome ‘hot regions’ for BP and being expressed in the brain. We reviewed published studies on the subject till December 2007. We precisely localized regions where positive linkage has been found, by the NCBI Map viewer (http://www.ncbi.nlm.nih.gov/mapview/); further, we identified genes located in interesting areas and expressed in the brain, by the Entrez gene, Unigene databases (http://www.ncbi.nlm.nih.gov/entrez/) and Human Protein Reference Database (http://www.hprd.org); these genes could be of interest in future investigations. The review of association studies gave interesting results, as a number of genes seem to be definitively involved in BP, such as SLC6A4, TPH2, DRD4, SLC6A3, DAOA, DTNBP1, NRG1, DISC1 and BDNF.
    [Show full text]
  • Regulation of P27kip1 and P57kip2 Functions by Natural Polyphenols
    biomolecules Review Regulation of p27Kip1 and p57Kip2 Functions by Natural Polyphenols Gian Luigi Russo 1,* , Emanuela Stampone 2 , Carmen Cervellera 1 and Adriana Borriello 2,* 1 National Research Council, Institute of Food Sciences, 83100 Avellino, Italy; [email protected] 2 Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 81031 Napoli, Italy; [email protected] * Correspondence: [email protected] (G.L.R.); [email protected] (A.B.); Tel.: +39-0825-299-331 (G.L.R.) Received: 31 July 2020; Accepted: 9 September 2020; Published: 13 September 2020 Abstract: In numerous instances, the fate of a single cell not only represents its peculiar outcome but also contributes to the overall status of an organism. In turn, the cell division cycle and its control strongly influence cell destiny, playing a critical role in targeting it towards a specific phenotype. Several factors participate in the control of growth, and among them, p27Kip1 and p57Kip2, two proteins modulating various transitions of the cell cycle, appear to play key functions. In this review, the major features of p27 and p57 will be described, focusing, in particular, on their recently identified roles not directly correlated with cell cycle modulation. Then, their possible roles as molecular effectors of polyphenols’ activities will be discussed. Polyphenols represent a large family of natural bioactive molecules that have been demonstrated to exhibit promising protective activities against several human diseases. Their use has also been proposed in association with classical therapies for improving their clinical effects and for diminishing their negative side activities. The importance of p27Kip1 and p57Kip2 in polyphenols’ cellular effects will be discussed with the aim of identifying novel therapeutic strategies for the treatment of important human diseases, such as cancers, characterized by an altered control of growth.
    [Show full text]