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
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
January-2020 Volume 56 Issue 1

Full Size Image

Cover Legend PDF

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
January-2020 Volume 56 Issue 1

Full Size Image

Cover Legend PDF

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

  • Supplementary Files
    • Supplementary_Data.pdf
Article

DNA methylation of GHSR, GNG4, HOXD9 and SALL3 is a common epigenetic alteration in thymic carcinoma

  • Authors:
    • Reina Kishibuchi
    • Kazuya Kondo
    • Shiho Soejima
    • Mitsuhiro Tsuboi
    • Koichiro Kajiura
    • Yukikiyo Kawakami
    • Naoya Kawakita
    • Toru Sawada
    • Hiroaki Toba
    • Mitsuteru Yoshida
    • Hiromitsu Takizawa
    • Akira Tangoku
  • View Affiliations / Copyright

    Affiliations: Department of Oncological Medical Services, Graduate School of Biomedical Sciences, Tokushima University, Tokushima 770‑8509, Japan, Department of Thoracic, Endocrine Surgery and Oncology, Graduate School of Biomedical Sciences, Tokushima University, Tokushima 770‑8503, Japan
  • Pages: 315-326
    |
    Published online on: November 18, 2019
       https://doi.org/10.3892/ijo.2019.4915
  • 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

Thymic epithelial tumors comprise thymoma, thymic carcinoma and neuroendocrine tumors of the thymus. Recent studies have revealed that the incidence of somatic non‑synonymous mutations is significantly higher in thymic carcinoma than in thymoma. However, limited information is currently available on epigenetic alterations in these types of cancer. In this study, we thus performed genome‑wide screening of aberrantly methylated CpG islands in thymoma and thymic carcinoma using Illumina HumanMethylation450 K BeadChip. We identified 92 CpG islands significantly hypermethylated in thymic carcinoma in relation to thymoma and selected G protein subunit gamma 4 (GNG4), growth hormone secretagogue receptor (GHSR), homeobox D9 (HOXD9) and spalt like transcription factor 3 (SALL3), which are related to cancer. We examined the promoter methylation of 4 genes in 46 thymic epithelial tumors and 20 paired thymus tissues using bisulfite pyrosequencing. Promoter methylation was significantly higher in thymic carcinoma than in thymoma and revealed a high discrimination between thymic carcinoma and thymoma in all 4 genes. Promoter methylation was higher in thymic carcinoma than in the thymus. No significant differences were observed in the promoter methylation of GNG4, HOXD9, or SALL3 between thymoma and the thymus. The promoter methylation of the 4 genes was not significantly higher in advanced‑stage tumors than in early‑stage tumors in all thymic epithelial tumors. Among the 4 genes, relapse‑free survival was significantly worse in tumors with a higher DNA methylation than in those with a lower DNA methylation in all thymic epithelial tumors. Moreover, relapse‑free survival was significantly worse in thymomas with a higher DNA methylation of HOXD9 and SALL3 than in those with a lower DNA methylation. On the whole, the findings of this study indicated that the promoter methylation of cancer‑related genes was significantly higher in thymic carcinoma than in thymoma and the thymus. This is a common epigenetic alteration of high diagnostic value in thymic carcinoma and may be involved in the carcinogenesis of thymic carcinoma. However, epigenetic alterations in the 3 genes, apart from GHSR, are not involved in the tumorigenesis of thymoma.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Kondo K: Therapy for thymic epithelial tumors. Gen Thorac Cardiovasc Surg. 62:468–474. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Travis WD, Brambilla E, Burke AP, Marx A and Nicholson AG: WHO classification of tumours of the lung, pleura, thymus and heart. World Health Organization classification of tumours. Bosman FT, Jaffe ES, Lakhani SR and Ohgaki H: 4th edition. IARC Press; Lyon: pp. 183–243. 2015

3 

Shimosato Y, Mukai K and Matsuno Y: Tumors of the mediastinum. AFIP Atlas of tumor pathology, Series 4. Armed Forces Institute of Pathology Washington, DC: 2010

4 

Wang Y, Thomas A, Lau C, Rajan A, Zhu Y, Killian JK, Petrini I, Pham T, Morrow B, Zhong X, et al: Mutations of epigenetic regulatory genes are common in thymic carcinomas. Sci Rep. 4:73362014. View Article : Google Scholar : PubMed/NCBI

5 

Radovich M, Pickering CR, Felau I, Ha G, Zhang H, Jo H, Hoadley KA, Anur P, Zhang J, McLellan M, et al: The integrated genomic landscape of thymic epithelial tumors. Cancer Cell. 33:244–258.e10. 2018. View Article : Google Scholar : PubMed/NCBI

6 

Petrini I, Meltzer PS, Kim IK, Lucchi M, Park KS, Fontanini G, Gao J, Zucali PA, Calabrese F, Favaretto A, et al: A specific missense mutation in GTF2I occurs at high frequency in thymic epithelial tumors. Nat Genet. 46:844–849. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Hirose Y, Kondo K, Takizawa H, Nagao T, Nakagawa Y, Fujino H, Taba H, Kenzaki K, Sakiyama S and Tangoku A: Aberrant methylation of tumour-related genes in thymic epithelial tumours. Lung Cancer. 64:155–159. 2009. View Article : Google Scholar

8 

Mokhtar M, Kondo K, Namura T, Ali AH, Fujita Y, Takai C, Takizawa H, Nakagawa Y, Toba H, Kajiura K, et al: Methylation and expression profiles of MGMT gene in thymic epithelial tumors. Lung Cancer. 83:279–287. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Detterbeck FC, Nicholson AG, Kondo K, Van Schil P and Moran C: The Masaoka-Koga stage classification for thymic malignancies: Clarification and definition of terms. J Thorac Oncol. 6(7 Suppl 3): S1710–S1716. 2011. View Article : Google Scholar : PubMed/NCBI

10 

Kajiura K, Masuda K, Naruto T, Kohmoto T, Watanabe M, Tsuboi M, Takizawa H, Kondo K, Tangoku A and Imoto I: Frequent silencing of the candidate tumor suppressor TRIM58 by promoter methylation in early-stage lung adenocarcinoma. Oncotarget. 8:2890–2905. 2017. View Article : Google Scholar :

11 

Moskalev EA, Jandaghi P, Fallah M, Manoochehri M, Botla SK, Kolychev OV, Nikitin EA, Bubnov VV, von Knebel Doeberitz M, Strobel O, et al: GHSR DNA hypermethylation is a common epigenetic alteration of high diagnostic value in a broad spectrum of cancers. Oncotarget. 6:4418–4427. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Pal J, Patil V, Mondal B, Shukla S, Hegde AS, Arivazhagan A, Santosh V and Somasundaram K: Epigenetically silenced GNG4 inhibits SDF1α/CXCR4 signaling in mesenchymal glioblastoma. Genes Cancer. 7:136–147. 2016.PubMed/NCBI

13 

Marzese DM, Scolyer RA, Huynh JL, Huang SK, Hirose H, Chong KK, Kiyohara E, Wang J, Kawas NP, Donovan NC, et al: Epigenome-wide DNA methylation landscape of melanoma progression to brain metastasis reveals aberrations on homeobox D cluster associated with prognosis. Hum Mol Genet. 23:226–238. 2014. View Article : Google Scholar

14 

Misawa K, Mochizuki D, Imai A, Misawa Y, Endo S, Mima M, Kawasaki H, Carey TE and Kanazawa T: Epigenetic silencing of SALL3 is an independent predictor of poor survival in head and neck cancer. Clin Epigenetics. 9:642017. View Article : Google Scholar :

15 

Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H and Kangawa K: Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 402:656–660. 1999. View Article : Google Scholar : PubMed/NCBI

16 

Howard AD, Feighner SD, Cully DF, Arena JP, Liberator PA, Rosenblum CI, Hamelin M, Hreniuk DL, Palyha OC, Anderson J, et al: A receptor in pituitary and hypothalamus that functions in growth hormone release. Science. 273:974–977. 1996. View Article : Google Scholar : PubMed/NCBI

17 

Lin TC and Hsiao M: Ghrelin and cancer progression. Biochim Biophys Acta Rev Cancer. 1868:51–57. 2017. View Article : Google Scholar : PubMed/NCBI

18 

Jandaghi P, Hoheisel JD and Riazalhosseini Y: GHSR hyper-methylation: A promising pan-cancer marker. Cell Cycle. 14:689–690. 2015. View Article : Google Scholar :

19 

Clapham DE and Neer EJ: G protein beta gamma subunits. Annu Rev Pharmacol Toxicol. 37:167–203. 1997. View Article : Google Scholar : PubMed/NCBI

20 

Maina EN, Morris MR, Zatyka M, Raval RR, Banks RE, Richards FM, Johnson CM and Maher ER: Identification of novel VHL target genes and relationship to hypoxic response pathways. Oncogene. 24:4549–4558. 2005. View Article : Google Scholar : PubMed/NCBI

21 

McGinnis W and Krumlauf R: Homeobox genes and axial patterning. Cell. 68:283–302. 1992. View Article : Google Scholar : PubMed/NCBI

22 

Shah N and Sukumar S: The Hox genes and their roles in oncogenesis. Nat Rev Cancer. 10:361–371. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Tabuse M, Ohta S, Ohashi Y, Fukaya R, Misawa A, Yoshida K, Kawase T, Saya H, Thirant C, Chneiweiss H, et al: Functional analysis of HOXD9 in human gliomas and glioma cancer stem cells. Mol Cancer. 10:602011. View Article : Google Scholar : PubMed/NCBI

24 

Lv X, Li L, Lv L, Qu X, Jin S, Li K, Deng X, Cheng L, He H and Dong L: HOXD9 promotes epithelial-mesenchymal transition and cancer metastasis by ZEB1 regulation in hepatocellular carcinoma. J Exp Clin Cancer Res. 34:1332015. View Article : Google Scholar : PubMed/NCBI

25 

Kohlhase J, Hausmann S, Stojmenovic G, Dixkens C, Bink K, Schulz-Schaeffer W, Altmann M and Engel W: SALL3, a new member of the human spalt-like gene family, maps to 18q23. Genomics. 62:216–222. 1999. View Article : Google Scholar : PubMed/NCBI

26 

Strathdee G, Sutherland R, Jonsson JJ, Sataloff R, Kohonen-Corish M, Grady D and Overhauser J: Molecular characterization of patients with 18q23 deletions. Am J Hum Genet. 60:860–868. 1997.PubMed/NCBI

27 

Yang XX, Sun JZ, Li FX, Wu YS, Du HY, Zhu W, Li XH and Li M: Aberrant methylation and downregulation of sall3 in human hepatocellular carcinoma. World J Gastroenterol. 18:2719–2726. 2012. View Article : Google Scholar : PubMed/NCBI

28 

Shikauchi Y, Saiura A, Kubo T, Niwa Y, Yamamoto J, Murase Y and Yoshikawa H: SALL3 interacts with DNMT3A and shows the ability to inhibit CpG island methylation in hepatocellular carcinoma. Mol Cell Biol. 29:1944–1958. 2009. View Article : Google Scholar : PubMed/NCBI

29 

Wei X, Zhang S, Cao D, Zhao M, Zhang Q, Zhao J, Yang T, Pei M, Wang L, Li Y and Yang X: Aberrant hypermethylation of SALL3 with HPV involvement contributes to the carcinogenesis of cervical cancer. PLoS One. 10:e01457002015. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Kishibuchi R, Kondo K, Soejima S, Tsuboi M, Kajiura K, Kawakami Y, Kawakita N, Sawada T, Toba H, Yoshida M, Yoshida M, et al: DNA methylation of GHSR, GNG4, HOXD9 and SALL3 is a common epigenetic alteration in thymic carcinoma. Int J Oncol 56: 315-326, 2020.
APA
Kishibuchi, R., Kondo, K., Soejima, S., Tsuboi, M., Kajiura, K., Kawakami, Y. ... Tangoku, A. (2020). DNA methylation of GHSR, GNG4, HOXD9 and SALL3 is a common epigenetic alteration in thymic carcinoma. International Journal of Oncology, 56, 315-326. https://doi.org/10.3892/ijo.2019.4915
MLA
Kishibuchi, R., Kondo, K., Soejima, S., Tsuboi, M., Kajiura, K., Kawakami, Y., Kawakita, N., Sawada, T., Toba, H., Yoshida, M., Takizawa, H., Tangoku, A."DNA methylation of GHSR, GNG4, HOXD9 and SALL3 is a common epigenetic alteration in thymic carcinoma". International Journal of Oncology 56.1 (2020): 315-326.
Chicago
Kishibuchi, R., Kondo, K., Soejima, S., Tsuboi, M., Kajiura, K., Kawakami, Y., Kawakita, N., Sawada, T., Toba, H., Yoshida, M., Takizawa, H., Tangoku, A."DNA methylation of GHSR, GNG4, HOXD9 and SALL3 is a common epigenetic alteration in thymic carcinoma". International Journal of Oncology 56, no. 1 (2020): 315-326. https://doi.org/10.3892/ijo.2019.4915
Copy and paste a formatted citation
x
Spandidos Publications style
Kishibuchi R, Kondo K, Soejima S, Tsuboi M, Kajiura K, Kawakami Y, Kawakita N, Sawada T, Toba H, Yoshida M, Yoshida M, et al: DNA methylation of GHSR, GNG4, HOXD9 and SALL3 is a common epigenetic alteration in thymic carcinoma. Int J Oncol 56: 315-326, 2020.
APA
Kishibuchi, R., Kondo, K., Soejima, S., Tsuboi, M., Kajiura, K., Kawakami, Y. ... Tangoku, A. (2020). DNA methylation of GHSR, GNG4, HOXD9 and SALL3 is a common epigenetic alteration in thymic carcinoma. International Journal of Oncology, 56, 315-326. https://doi.org/10.3892/ijo.2019.4915
MLA
Kishibuchi, R., Kondo, K., Soejima, S., Tsuboi, M., Kajiura, K., Kawakami, Y., Kawakita, N., Sawada, T., Toba, H., Yoshida, M., Takizawa, H., Tangoku, A."DNA methylation of GHSR, GNG4, HOXD9 and SALL3 is a common epigenetic alteration in thymic carcinoma". International Journal of Oncology 56.1 (2020): 315-326.
Chicago
Kishibuchi, R., Kondo, K., Soejima, S., Tsuboi, M., Kajiura, K., Kawakami, Y., Kawakita, N., Sawada, T., Toba, H., Yoshida, M., Takizawa, H., Tangoku, A."DNA methylation of GHSR, GNG4, HOXD9 and SALL3 is a common epigenetic alteration in thymic carcinoma". International Journal of Oncology 56, no. 1 (2020): 315-326. https://doi.org/10.3892/ijo.2019.4915
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