Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
October-2018 Volume 40 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
October-2018 Volume 40 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Identification of the potential molecular mechanism and driving mutations in the pathogenesis of familial intestinal gastric cancer by whole exome sequencing

  • Authors:
    • Haixiang Chen
    • Juan Wang
    • Yi Zhuang
    • Hao Wu
  • View Affiliations / Copyright

    Affiliations: Department of Medical Records, The Third Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210001, P.R. China, Department of General Surgery, Xi Jing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, Department of Respiratory Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China, Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
  • Pages: 2316-2324
    |
    Published online on: August 1, 2018
       https://doi.org/10.3892/or.2018.6613
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The genetic alterations in familial intestinal gastric cancer (FIGC) have not been clearly understood. Aiming to explore the molecular basis and the driving mutations underlying the pathogenesis of FIGC, we performed exome sequencing of the blood samples of the members of an extended family with FIGC. The differences in mutation patterns between family members with gastric cancer and controls were analysed and the overlapped variants were screened by comparing previously published data for blood and tumours from gastric cancer patients. The overlapped genes harbouring insertions‑deletions (INDELs) and single‑nucleotide variants (SNVs) were subjected to function, pathway and network analysis. The INDELs were enriched in DNA packaging and in the neurological system process related to the biological process (BP), while SNVs were closely related to cell‑function‑related BPs. ESR was the significant node with marked centrality in the SNV network. ERK 1/2 was the hub node in the INDEL network, interacting with EZK and IGF2R. Sequencing analysis revealed ESR1 homozygous mutations in exon 1 (216G > C) and exon 10 (2234C > T) and EZR1 heterozygous deletion of 68‑69 GT nucleotides in exon 13 of the family members. The IGF2R gene only demonstrated a mutation in exon 48 of the propositus. All hub proteins had direct or indirect interactions in the protein‑protein interaction network.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Rugge M, Fassan M and Graham DY: Epidemiology of Gastric Cancer. Springer International Publishing; pp. 23–34. 2015, PubMed/NCBI

2 

Yaghoobi M, Bijarchi R and Narod SA: Family history and the risk of gastric cancer. Br J Cancer. 102:237–242. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Vogelaar IP, van der Post RS, Bisseling TM, van Krieken JHJ, Ligtenberg MJ and Hoogerbrugge N: Familial gastric cancer: Detection of a hereditary cause helps to understand its etiology. Hered Cancer Clin Pract. 10:182012. View Article : Google Scholar : PubMed/NCBI

4 

Caldas C, Carneiro F, Lynch HT, Yokota J, Wiesner GL, Powell SM, Lewis FR, Huntsman DG, Pharoah PD, Jankowski JA, et al: Familial gastric cancer: Overview and guidelines for management. J Med Genet. 36:873–880. 1999.PubMed/NCBI

5 

Carneiro F: Hereditary gastric cancer. Pathologe. 33 Suppl 2:S231–S234. 2012. View Article : Google Scholar

6 

Oliveira C, Pinheiro H, Figueiredo J, Seruca R and Carneiro F: Familial gastric cancer: Genetic susceptibility, pathology, and implications for management. Lancet Oncol. 16:e60–e70. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Nagarajan N, Bertrand D, Hillmer AM, Zang ZJ, Yao F, Jacques PÉ, Teo AS, Cutcutache I, Zhang Z, Lee WH, et al: Whole-genome reconstruction and mutational signatures in gastric cancer. Genome Biol. 13:R1152012. View Article : Google Scholar : PubMed/NCBI

8 

Suleiman SH, Koko ME, Nasir WH, Elfateh O, Elgizouli UK, Abdallah MO, Alfarouk KO, Hussain A, Faisal S, Ibrahim FM, et al: Exome sequencing of a colorectal cancer family reveals shared mutation pattern and predisposition circuitry along tumor pathways. Front Genet. 6:2882015. View Article : Google Scholar : PubMed/NCBI

9 

Sommer S and Fuqua SA: Estrogen receptor and breast cancer. Semin Cancer Biol. 11:339–352. 2001. View Article : Google Scholar : PubMed/NCBI

10 

Schaffer BS, Lin MF, Byrd JC, Park JH and MacDonald RG: Opposing roles for the insulin-like growth factor (IGF)-II and mannose 6-phosphate (Man-6-P) binding activities of the IGF-II/Man-6-P receptor in the growth of prostate cancer cells. Endocrinology. 144:955–966. 2003. View Article : Google Scholar : PubMed/NCBI

11 

Vaheri A, Carpén O, Heiska L, Helander TS, Jääskeläinen J, Majander-Nordenswan P, Sainio M, Timonen T and Turunen O: The ezrin protein family: Membrane-cytoskeleton interactions and disease associations. Curr Opin Cell Biol. 9:659–666. 1997. View Article : Google Scholar : PubMed/NCBI

12 

Krämer A, Green J, Pollard J Jr and Tugendreich S: Causal analysis approaches in Ingenuity Pathway Analysis. Bioinformatics. 30:523–530. 2014. View Article : Google Scholar : PubMed/NCBI

13 

Breitkreutz BJ, Stark C and Tyers M: Osprey: A network visualization system. Genome Biol. 4:R222003. View Article : Google Scholar : PubMed/NCBI

14 

Gasteiger E, Gattiker A, Hoogland C, Ivanyi I, Appel RD and Bairoch A: ExPASy: The proteomics server for in-depth protein knowledge and analysis. Nucleic Acids Res. 31:3784–3788. 2003. View Article : Google Scholar : PubMed/NCBI

15 

Pirooznia M, Nagarajan V and Deng Y: GeneVenn - A web application for comparing gene lists using Venn diagrams. Bioinformation. 1:420–422. 2007. View Article : Google Scholar : PubMed/NCBI

16 

Bernini M, Barbi S, Roviello F, Scarpa A, Moore P, Pedrazzani C, Beghelli S, Marrelli D and de Manzoni G: Family history of gastric cancer: A correlation between epidemiologic findings and clinical data. Gastric Cancer. 9:9–13. 2006. View Article : Google Scholar : PubMed/NCBI

17 

Filipe MI, Potet F, Bogomoletz WV, Dawson PA, Fabiani B, Chauveinc P, Fenzy A, Gazzard B, Goldfain D and Zeegen R: Incomplete sulphomucin-secreting intestinal metaplasia for gastric cancer. Preliminary data from a prospective study from three centres. Gut. 26:1319–1326. 1985. View Article : Google Scholar : PubMed/NCBI

18 

Cassaro M, Rugge M, Gutierrez O, Leandro G, Graham DY and Genta RM: Topographic patterns of intestinal metaplasia and gastric cancer. Am J Gastroenterol. 95:1431–1438. 2000. View Article : Google Scholar : PubMed/NCBI

19 

Ghosh A, Hartge P, Purdue MP, Chanock SJ, Amundadottir L, Wang Z, Wentzensen N, Chatterjee N and Wacholder S: Assessing disease risk in genome-wide association studies using family history. Epidemiology. 23:616–622. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Cavalli V, Vilbois F, Corti M, Marcote MJ, Tamura K, Karin M, Arkinstall S and Gruenberg J: The stress-induced MAP kinase p38 regulates endocytic trafficking via the GDI: Rab5 complex. Mol Cell. 7:421–432. 2001. View Article : Google Scholar : PubMed/NCBI

21 

Junttila MR, Li SP and Westermarck J: Phosphatase-mediated crosstalk between MAPK signaling pathways in the regulation of cell survival. FASEB J. 22:954–965. 2008. View Article : Google Scholar : PubMed/NCBI

22 

Reddy KB, Nabha SM and Atanaskova N: Role of MAP kinase in tumor progression and invasion. Cancer Metastasis Rev. 22:395–403. 2003. View Article : Google Scholar : PubMed/NCBI

23 

Dhillon AS, Hagan S, Rath O and Kolch W: MAP kinase signalling pathways in cancer. Oncogene. 26:3279–3290. 2007. View Article : Google Scholar : PubMed/NCBI

24 

Chimento A, Sirianni R, Casaburi I, Ruggiero C, Maggiolini M, Andò S and Pezzi V: 17β-Estradiol activates GPER- and ESR1-dependent pathways inducing apoptosis in GC-2 cells, a mouse spermatocyte-derived cell line. Mol Cell Endocrinol. 355:49–59. 2012. View Article : Google Scholar : PubMed/NCBI

25 

Buchanan CM, Phillips AR and Cooper GJ: A novel two-chain IGF-II-derived peptide from purified β-cell granules. Growth Horm IGF Res. 20:360–366. 2010. View Article : Google Scholar : PubMed/NCBI

26 

Khanna C, Wan X, Bose S, Cassaday R, Olomu O, Mendoza A, Yeung C, Gorlick R, Hewitt SM and Helman LJ: The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis. Nat Med. 10:182–186. 2004. View Article : Google Scholar : PubMed/NCBI

27 

Roberts PJ and Der CJ: Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene. 26:3291–3310. 2007. View Article : Google Scholar : PubMed/NCBI

28 

Robinson DR, Wu YM, Vats P, Su F, Lonigro RJ, Cao X, Kalyana - Sundaram S, Wang R, Ning Y, Hodges L, et al: Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat Genet. 45:1446–1451. 2013. View Article : Google Scholar : PubMed/NCBI

29 

Toy W, Shen Y, Won H, Green B, Sakr RA, Will M, Li Z, Gala K, Fanning S, King TA, et al: ESR1 ligand-binding domain mutations in hormone-resistant breast cancer. Nat Genet. 45:1439–1445. 2013. View Article : Google Scholar : PubMed/NCBI

30 

Schiavon G, Hrebien S, Garcia-Murillas I, Cutts RJ, Pearson A, Tarazona N, Fenwick K, Kozarewa I, Lopez-Knowles E, Ribas R, et al: Analysis of ESR1 mutation in circulating tumor DNA demonstrates evolution during therapy for metastatic breast cancer. Sci Transl Med. 7:313ra1822015. View Article : Google Scholar : PubMed/NCBI

31 

Woo IS, Park MJ, Choi SW, Kim SJ, Lee MA, Kang JH, Hong YS and Lee KS: Loss of estrogen receptor-alpha expression is associated with hypermethylation near its ATG start codon in gastric cancer cell lines. Oncol Rep. 11:617–622. 2004.PubMed/NCBI

32 

Kong FM, Anscher MS, Washington MK, Killian JK and Jirtle RL: M6P/IGF2R is mutated in squamous cell carcinoma of the lung. Oncogene. 19:1572–1578. 2000. View Article : Google Scholar : PubMed/NCBI

33 

Oka Y, Waterland RA, Killian JK, Nolan CM, Jang HS, Tohara K, Sakaguchi S, Yao T, Iwashita A, Yata Y, et al: M6P/IGF2R tumor suppressor gene mutated in hepatocellular carcinomas in Japan. Hepatology. 35:1153–1163. 2002. View Article : Google Scholar : PubMed/NCBI

34 

Yamada T, De Souza AT, Finkelstein S and Jirtle RL: Loss of the gene encoding mannose 6-phosphate/insulin-like growth factor II receptor is an early event in liver carcinogenesis. Proc Natl Acad Sci USA. 94:10351–10355. 1997. View Article : Google Scholar : PubMed/NCBI

35 

De Souza AT, Hankins GR, Washington MK, Orton TC and Jirtle RL: M6P/IGF2R gene is mutated in human hepatocellular carcinomas with loss of heterozygosity. Nat Genet. 11:447–449. 1995. View Article : Google Scholar : PubMed/NCBI

36 

Hankins GR, De Souza AT, Bentley RC, Patel MR, Marks JR, Iglehart JD and Jirtle RL: M6P/IGF2 receptor: A candidate breast tumor suppressor gene. Oncogene. 12:2003–2009. 1996.PubMed/NCBI

37 

Yu H and Rohan T: Role of the insulin-like growth factor family in cancer development and progression. J Natl Cancer Inst. 92:1472–1489. 2000. View Article : Google Scholar : PubMed/NCBI

38 

Mäkitie T, Carpén O, Vaheri A and Kivelä T: Ezrin as a prognostic indicator and its relationship to tumor characteristics in uveal malignant melanoma. Invest Ophthalmol Vis Sci. 42:2442–2449. 2001.PubMed/NCBI

39 

Hirota WK, Zuckerman MJ, Adler DG, Davila RE, Egan J, Leighton JA, Qureshi WA, Rajan E, Fanelli R, Wheeler-Harbaugh J, et al: Standards of Practice Committee, American Society for Gastrointestinal Endoscopy: ASGE guideline: The role of endoscopy in the surveillance of premalignant conditions of the upper GI tract. Gastrointest Endosc. 63:570–580. 2006. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Chen H, Wang J, Zhuang Y and Wu H: Identification of the potential molecular mechanism and driving mutations in the pathogenesis of familial intestinal gastric cancer by whole exome sequencing. Oncol Rep 40: 2316-2324, 2018.
APA
Chen, H., Wang, J., Zhuang, Y., & Wu, H. (2018). Identification of the potential molecular mechanism and driving mutations in the pathogenesis of familial intestinal gastric cancer by whole exome sequencing. Oncology Reports, 40, 2316-2324. https://doi.org/10.3892/or.2018.6613
MLA
Chen, H., Wang, J., Zhuang, Y., Wu, H."Identification of the potential molecular mechanism and driving mutations in the pathogenesis of familial intestinal gastric cancer by whole exome sequencing". Oncology Reports 40.4 (2018): 2316-2324.
Chicago
Chen, H., Wang, J., Zhuang, Y., Wu, H."Identification of the potential molecular mechanism and driving mutations in the pathogenesis of familial intestinal gastric cancer by whole exome sequencing". Oncology Reports 40, no. 4 (2018): 2316-2324. https://doi.org/10.3892/or.2018.6613
Copy and paste a formatted citation
x
Spandidos Publications style
Chen H, Wang J, Zhuang Y and Wu H: Identification of the potential molecular mechanism and driving mutations in the pathogenesis of familial intestinal gastric cancer by whole exome sequencing. Oncol Rep 40: 2316-2324, 2018.
APA
Chen, H., Wang, J., Zhuang, Y., & Wu, H. (2018). Identification of the potential molecular mechanism and driving mutations in the pathogenesis of familial intestinal gastric cancer by whole exome sequencing. Oncology Reports, 40, 2316-2324. https://doi.org/10.3892/or.2018.6613
MLA
Chen, H., Wang, J., Zhuang, Y., Wu, H."Identification of the potential molecular mechanism and driving mutations in the pathogenesis of familial intestinal gastric cancer by whole exome sequencing". Oncology Reports 40.4 (2018): 2316-2324.
Chicago
Chen, H., Wang, J., Zhuang, Y., Wu, H."Identification of the potential molecular mechanism and driving mutations in the pathogenesis of familial intestinal gastric cancer by whole exome sequencing". Oncology Reports 40, no. 4 (2018): 2316-2324. https://doi.org/10.3892/or.2018.6613
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team