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
2014-March Volume 31 Issue 3

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
2014-March Volume 31 Issue 3

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

A novel somatic FGFR3 mutation in primary lung cancer

  • Authors:
    • Kazuya Shinmura
    • Hisami Kato
    • Shun Matsuura
    • Yusuke Inoue
    • Hisaki Igarashi
    • Kiyoko Nagura
    • Satoki Nakamura
    • Kyoko Maruyama
    • Mari Tajima
    • Kazuhito Funai
    • Hiroshi Ogawa
    • Masayuki Tanahashi
    • Hiroshi Niwa
    • Haruhiko Sugimura
  • View Affiliations / Copyright

    Affiliations: Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan, Department of Surgery 1, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan, Division of Pathology, Respiratory Disease Center, Seirei Mikatahara General Hospital, Hamamatsu, Shizuoka 433-8558, Japan, Division of Thoracic Surgery, Respiratory Disease Center, Seirei Mikatahara General Hospital, Hamamatsu, Shizuoka 433-8558, Japan
  • Pages: 1219-1224
    |
    Published online on: January 20, 2014
       https://doi.org/10.3892/or.2014.2984
  • 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 recent discovery of mutations and fusions of oncokinase genes in a subset of lung cancers (LCs) is of considerable clinical interest, since LCs containing such mutations or fusion transcripts are reportedly sensitive to kinase inhibitors. To better understand the role of the recently identified fibroblast growth factor receptor 3 (FGFR3) mutations and fusions in pulmonary carcinogenesis, we examined 214 LCs for mutations in the mutation cluster region of the FGFR3 gene using sequencing analysis. We also examined 190 LCs for the FGFR3-TACC3 and FGFR3-BAIAP2L1 fusion transcripts using reverse transcription-polymerase chain reaction (RT-PCR) analysis. Although the expression of FGFR3-TACC3 and FGFR3-BAIAP2L1 fusion transcripts was not detected in any of the carcinomas, somatic FGFR3 mutations were detected in two (0.9%) LCs. The two mutations were the same, i.e., p.R248H. That was a novel mutation occurring in the same codon as p.R248C, for which an oncogenic potential has previously been shown. Increased FGFR3 expression was shown in the two LCs containing the FGFR3 p.R248H mutation using qPCR. Histologically, both carcinomas were squamous cell carcinomas, therefore the incidence of the FGFR3 mutation among the squamous cell carcinoma cases was calculated as 3.2% (2/63). When we examined other co-occurring genetic abnormalities, one case exhibited a p53 p.R273C mutation, while the other case exhibited PIK3CA and SOX2 amplifications. The above results suggest that an FGFR3 p.R248H mutation is involved in the carcinogenesis of a subset of LCs and may contribute to the elucidation of the characteristics of FGFR3 mutation-positive LCs in the future.
View Figures

Figure 1

Figure 2

View References

1 

Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, Fujiwara S, Watanabe H, Kurashina K, Hatanaka H, Bando M, Ohno S, Ishikawa Y, Aburatani H, Niki T, Sohara Y, Sugiyama Y and Mano H: Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 448:561–566. 2007.PubMed/NCBI

2 

Shinmura K, Kageyama S, Tao H, Bunai T, Suzuki M, Kamo T, Takamochi K, Suzuki K, Tanahashi M, Niwa H, Ogawa H and Sugimura H: EML4-ALK fusion transcripts, but no NPM-, TPM3-, CLTC-, ATIC-, or TFG-ALK fusion transcripts, in non-small cell lung carcinomas. Lung Cancer. 61:163–169. 2008. View Article : Google Scholar : PubMed/NCBI

3 

Schmid K, Oehl N, Wrba F, Pirker R, Pirker C and Filipits M: EGFR/KRAS/BRAF mutations in primary lung adenocarcinomas and corresponding locoregional lymph node metastases. Clin Cancer Res. 15:4554–4560. 2009. View Article : Google Scholar

4 

Kohno T, Ichikawa H, Totoki Y, Yasuda K, Hiramoto M, Nammo T, Sakamoto H, Tsuta K, Furuta K, Shimada Y, Iwakawa R, Ogiwara H, Oike T, Enari M, Schetter AJ, Okayama H, Haugen A, Skaug V, Chiku S, Yamanaka I, Arai Y, Watanabe S, Sekine I, Ogawa S, Harris CC, Tsuda H, Yoshida T, Yokota J and Shibata T: KIF5B-RET fusions in lung adenocarcinoma. Nat Med. 18:375–377. 2012. View Article : Google Scholar

5 

Takeuchi K, Soda M, Togashi Y, Suzuki R, Sakata S, Hatano S, Asaka R, Hamanaka W, Ninomiya H, Uehara H, Lim Choi Y, Satoh Y, Okumura S, Nakagawa K, Mano H and Ishikawa Y: RET, ROS1 and ALK fusions in lung cancer. Nat Med. 18:378–381. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Lipson D, Capelletti M, Yelensky R, Otto G, Parker A, Jarosz M, Curran JA, Balasubramanian S, Bloom T, Brennan KW, Donahue A, Downing SR, Frampton GM, Garcia L, Juhn F, Mitchell KC, White E, White J, Zwirko Z, Peretz T, Nechushtan H, Soussan-Gutman L, Kim J, Sasaki H, Kim HR, Park SI, Ercan D, Sheehan CE, Ross JS, Cronin MT, Jänne PA and Stephens PJ: Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies. Nat Med. 18:382–384. 2012.

7 

Matsuura S, Shinmura K, Kamo T, Igarashi H, Maruyama K, Tajima M, Ogawa H, Tanahashi M, Niwa H, Funai K, Kohno T, Suda T and Sugimura H: CD74-ROS1 fusion transcripts in resected non-small cell lung carcinoma. Oncol Rep. 30:1675–1680. 2013.PubMed/NCBI

8 

Oxnard GR, Binder A and Jänne PA: New targetable oncogenes in non-small-cell lung cancer. J Clin Oncol. 31:1097–1104. 2013. View Article : Google Scholar : PubMed/NCBI

9 

Casaluce F, Sgambato A, Maione P, Rossi A, Ferrara C, Napolitano A, Palazzolo G, Ciardiello F and Gridelli C: ALK inhibitors: a new targeted therapy in the treatment of advanced NSCLC. Target Oncol. 8:55–67. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Cappellen D, De Oliveira C, Ricol D, de Medina S, Bourdin J, Sastre-Garau X, Chopin D, Thiery JP and Radvanyi F: Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas. Nat Genet. 23:18–20. 1999. View Article : Google Scholar : PubMed/NCBI

11 

Greulich H and Pollock PM: Targeting mutant fibroblast growth factor receptors in cancer. Trends Mol Med. 17:283–292. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Cancer Genome Atlas Research Network. Comprehensive genomic characterization of squamous cell lung cancers. Nature. 489:519–525. 2012. View Article : Google Scholar : PubMed/NCBI

13 

Singh D, Chan JM, Zoppoli P, Niola F, Sullivan R, Castano A, Liu EM, Reichel J, Porrati P, Pellegatta S, Qiu K, Gao Z, Ceccarelli M, Riccardi R, Brat DJ, Guha A, Aldape K, Golfinos JG, Zagzag D, Mikkelsen T, Finocchiaro G, Lasorella A, Rabadan R and Iavarone A: Transforming fusions of FGFR and TACC genes in human glioblastoma. Science. 337:1231–1235. 2012.PubMed/NCBI

14 

Williams SV, Hurst CD and Knowles MA: Oncogenic FGFR3 gene fusions in bladder cancer. Hum Mol Genet. 22:795–803. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Wu YM, Su F, Kalyana-Sundaram S, Khazanov N, Ateeq B, Cao X, Lonigro RJ, Vats P, Wang R, Lin SF, Cheng AJ, Kunju LP, Siddiqui J, Tomlins SA, Wyngaard P, Sadis S, Roychowdhury S, Hussain MH, Feng FY, Zalupski MM, Talpaz M, Pienta KJ, Rhodes DR, Robinson DR and Chinnaiyan AM: Identification of targetable FGFR gene fusions in diverse cancers. Cancer Discov. 3:636–647. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Majewski IJ, Mittempergher L, Davidson NM, Bosma A, Willems SM, Horlings HM, de Rink I, Greger L, Hooijer GK, Peters D, Nederlof PM, Hofland I, de Jong J, Wesseling J, Kluin RJ, Brugman W, Kerkhoven R, Nieboer F, Roepman P, Broeks A, Muley TR, Jassem J, Niklinski J, van Zandwijk N, Brazma A, Oshlack A, van den Heuvel M and Bernards R: Identification of recurrent FGFR3 fusion genes in lung cancer through kinome-centred RNA sequencing. J Pathol. 230:270–276. 2013.

17 

Liao RG, Jung J, Tchaicha J, Wilkerson MD, Sivachenko A, Beauchamp EM, Liu Q, Pugh TJ, Pedamallu CS, Hayes DN, Gray NS, Getz G, Wong KK, Haddad RI, Meyerson M and Hammerman PS: Inhibitor-sensitive FGFR2 and FGFR3 mutations in lung squamous cell carcinoma. Cancer Res. 73:5195–5205. 2013. View Article : Google Scholar : PubMed/NCBI

18 

Shinmura K, Goto M, Suzuki M, Tao H, Yamada H, Igarashi H, Matsuura S, Maeda M, Konno H, Matsuda T and Sugimura H: Reduced expression of MUTYH with suppressive activity against mutations caused by 8-hydroxyguanine is a novel predictor of a poor prognosis in human gastric cancer. J Pathol. 225:414–423. 2011. View Article : Google Scholar : PubMed/NCBI

19 

Pao W and Girard N: New driver mutations in non-small-cell lung cancer. Lancet Oncol. 12:175–180. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Ulivi P, Romagnoli M, Chiadini E, Casoni GL, Capelli L, Gurioli C, Zoli W, Saragoni L, Dubini A, Tesei A, Amadori D and Poletti V: Assessment of EGFR and K-ras mutations in fixed and fresh specimens from transesophageal ultrasound-guided fine needle aspiration in non-small cell lung cancer patients. Int J Oncol. 41:147–152. 2012.

21 

Mantripragada K and Khurshid H: Targeting genomic alterations in squamous cell lung cancer. Front Oncol. 3:1952013. View Article : Google Scholar : PubMed/NCBI

22 

Pros E, Lantuejoul S, Sanchez-Verde L, Castillo SD, Bonastre E, Suarez-Gauthier A, Conde E, Cigudosa JC, Lopez-Rios F, Torres-Lanzas J, Castellví J, Ramon y Cajal S, Brambilla E and Sanchez-Cespedes M: Determining the profiles and parameters for gene amplification testing of growth factor receptors in lung cancer. Int J Cancer. 133:898–907. 2013. View Article : Google Scholar : PubMed/NCBI

23 

Intini D, Baldini L, Fabris S, Lombardi L, Ciceri G, Maiolo AT and Neri A: Analysis of FGFR3 gene mutations in multiple myeloma patients with t(4;14). Br J Haematol. 114:362–364. 2001.

24 

Petitjean A, Mathe E, Kato S, Ishioka C, Tavtigian SV, Hainaut P and Olivier M: Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database. Hum Mutat. 28:622–629. 2007.PubMed/NCBI

25 

Yeudall WA, Vaughan CA, Miyazaki H, Ramamoorthy M, Choi MY, Chapman CG, Wang H, Black E, Bulysheva AA, Deb SP, Windle B and Deb S: Gain-of-function mutant p53 upregulates CXC chemokines and enhances cell migration. Carcinogenesis. 33:442–451. 2012. View Article : Google Scholar : PubMed/NCBI

26 

Bromberg Y and Rost B: SNAP: predict effect of non-synonymous polymorphisms on function. Nucleic Acids Res. 35:3823–3835. 2007. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Shinmura K, Kato H, Matsuura S, Inoue Y, Igarashi H, Nagura K, Nakamura S, Maruyama K, Tajima M, Funai K, Funai K, et al: A novel somatic FGFR3 mutation in primary lung cancer. Oncol Rep 31: 1219-1224, 2014.
APA
Shinmura, K., Kato, H., Matsuura, S., Inoue, Y., Igarashi, H., Nagura, K. ... Sugimura, H. (2014). A novel somatic FGFR3 mutation in primary lung cancer. Oncology Reports, 31, 1219-1224. https://doi.org/10.3892/or.2014.2984
MLA
Shinmura, K., Kato, H., Matsuura, S., Inoue, Y., Igarashi, H., Nagura, K., Nakamura, S., Maruyama, K., Tajima, M., Funai, K., Ogawa, H., Tanahashi, M., Niwa, H., Sugimura, H."A novel somatic FGFR3 mutation in primary lung cancer". Oncology Reports 31.3 (2014): 1219-1224.
Chicago
Shinmura, K., Kato, H., Matsuura, S., Inoue, Y., Igarashi, H., Nagura, K., Nakamura, S., Maruyama, K., Tajima, M., Funai, K., Ogawa, H., Tanahashi, M., Niwa, H., Sugimura, H."A novel somatic FGFR3 mutation in primary lung cancer". Oncology Reports 31, no. 3 (2014): 1219-1224. https://doi.org/10.3892/or.2014.2984
Copy and paste a formatted citation
x
Spandidos Publications style
Shinmura K, Kato H, Matsuura S, Inoue Y, Igarashi H, Nagura K, Nakamura S, Maruyama K, Tajima M, Funai K, Funai K, et al: A novel somatic FGFR3 mutation in primary lung cancer. Oncol Rep 31: 1219-1224, 2014.
APA
Shinmura, K., Kato, H., Matsuura, S., Inoue, Y., Igarashi, H., Nagura, K. ... Sugimura, H. (2014). A novel somatic FGFR3 mutation in primary lung cancer. Oncology Reports, 31, 1219-1224. https://doi.org/10.3892/or.2014.2984
MLA
Shinmura, K., Kato, H., Matsuura, S., Inoue, Y., Igarashi, H., Nagura, K., Nakamura, S., Maruyama, K., Tajima, M., Funai, K., Ogawa, H., Tanahashi, M., Niwa, H., Sugimura, H."A novel somatic FGFR3 mutation in primary lung cancer". Oncology Reports 31.3 (2014): 1219-1224.
Chicago
Shinmura, K., Kato, H., Matsuura, S., Inoue, Y., Igarashi, H., Nagura, K., Nakamura, S., Maruyama, K., Tajima, M., Funai, K., Ogawa, H., Tanahashi, M., Niwa, H., Sugimura, H."A novel somatic FGFR3 mutation in primary lung cancer". Oncology Reports 31, no. 3 (2014): 1219-1224. https://doi.org/10.3892/or.2014.2984
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