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
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
May-2015 Volume 9 Issue 5

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
May-2015 Volume 9 Issue 5

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

Intra‑tumor heterogeneity of BRAF V600E mutation in lung adenocarcinomas

  • Authors:
    • Tsutomu Tatematsu
    • Hidefumi Sasaki
    • Shigeki Shimizu
    • Yu Hikosaka
    • Katsuhiro Okuda
    • Hiroshi Haneda
    • Satoru Moriyama
    • Motoki Yano
    • Yoshitaka Fujii
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 467‑8601, Japan, Department of Pathology, Hyogo College of Medicine, Nishinomiya, Hyogo 663‑8501, Japan
  • Pages: 1719-1722
    |
    Published online on: February 17, 2015
       https://doi.org/10.3892/etm.2015.2298
  • 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

BRAF mutations exist in numerous types of cancer, including melanomas, colorectal cancers and lung cancers. The V600E‑specific inhibitor vemurafenib has marked clinical activity in patients with BRAF V600E‑mutated melanoma. However, there are many cases of resistance to vemurafenib. This may be due to the reported intra‑tumor heterogeneity of the BRAF V600E mutation in primary melanomas. BRAF mutations are found in 1‑5% of non‑small cell carcinomas (NSCLCs), almost exclusively in adenocarcinoma. A few cases have been reported in which vemurafenib was effective against BRAF V600E‑mutated lung cancers. In a previous study, five lung adenocarcinomas with BRAF V600E mutation were detected by direct sequencing. The present study analyzed these tumors for the percentage of mutation (%mutation) by competitive allele‑specific polymerase chain reaction (CAST‑PCR) assay. In addition, sections of all components of the adenocarcinomas were obtained by laser microdissection and analyzed. The %mutations of BRAF V600E within the macrodissected tumors (cases 1‑5) were: Case 1, 10.0%; case 2, 8.0%; case 3, 8.9%; case 4, 21.5%; and case 5, 14.9%. In four cases (cases 2‑5), the %mutations of each adenocarcinoma component were as follows: Case 2, lepidic growth 6.5‑24.5%, papillary 1.3‑11.2% and acinar 9.8%; case 3, solid 2.5‑69.9%, acinar 12.4‑27.1% and papillary 3.7‑17.4%; case 4, acinar 10.0‑45.0% and papillary 44.0%; and case 5, papillary 3.7‑93.4%. Sensitive BRAF mutation detection methods were used and evidence for heterogeneity of the BRAF V600E mutation in these lung adenocarcinoma cases was observed. Targeted therapy with a BRAF V600E inhibitor such as vemurafenib may have potential in the treatment of lung cancer with this mutation; however, it is necessary to consider how the treatment effect of and drug resistance to BRAF V600E inhibitors are affected by the presence of heterogeneity in future studies.
View Figures
View References

1 

Ginsberg RJ, Kris K and Armstrong G: Cancer of the lungCancer: Principles and practice of oncology. De Vita VT Jr, Hellman S and Rosenberg SA: 4th. Lippincott, Philadelphia: pp. 673–682. 1993

2 

Travis WD, Travis LB and Devesa SS: Lung cancer. Cancer. 75 (Suppl S1):191–202. 1995. View Article : Google Scholar : PubMed/NCBI

3 

Paez JG, Jänne PA, Lee JC, et al: EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 304:1497–1500. 2004. View Article : Google Scholar : PubMed/NCBI

4 

Sasaki H, Shimizu S, Endo K, et al: EGFR and erbB2 mutation status in Japanese lung cancer patients. Int J Cancer. 118:180–184. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Fukuoka M, Wu YL, Thongprasert S, et al: Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J Clin Oncol. 29:2866–2874. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Soda M, Choi YL, Enomoto M, et al: Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 448:561–566. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Peyssonnaux C and Eychène A: The Raf/MEK/ERK pathway: new concepts of activation. Biol Cell. 93:53–62. 2001. View Article : Google Scholar : PubMed/NCBI

8 

Davies H, Bignell GR, Cox C, et al: Mutations of the BRAF gene in human cancer. Nature. 417:949–954. 2002. View Article : Google Scholar : PubMed/NCBI

9 

Flaherty KT, Puzanov I, Kim KB, et al: Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med. 363:809–819. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Chapman PB, Hauschild A, Robert C, et al: BRIM-3 Study Group: Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 364:2507–2516. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Yancovitz M, Litterman A, Yoon J, et al: Intra- and inter-tumor heterogeneity of BRAFV600E mutations in primary and metastatic melanoma. PLoS One. 7:e293362012. View Article : Google Scholar : PubMed/NCBI

12 

Marchetti A, Felicioni L, Malatesta S, et al: Clinical features and outcome of patients with non-small-cell lung cancer harboring BRAF mutations. J Clin Oncol. 29:3574–3579. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Paik PK, Arcila ME, Fara M, et al: Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. J Clin Oncol. 29:2046–2051. 2011. View Article : Google Scholar : PubMed/NCBI

14 

Peters S, Michielin O and Zimmermann S: Dramatic response induced by vemurafenib in a BRAF V600E-mutated lung adenocarcinoma. J Clin Oncol. 31:e341–e344. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Gautschi O, Pauli C, Strobel K, et al: A patient with BRAF V600E lung adenocarcinoma responding to vemurafenib. J Thorac Oncol. 7:e23–e24. 2012. View Article : Google Scholar : PubMed/NCBI

16 

Sasaki H, Shitara M, Yokota K, et al: Braf and erbB2 mutations correlate with smoking status in lung cancer patients. Exp Ther Med. 3:771–775. 2012.PubMed/NCBI

17 

Sasaki H, Shimizu S, Tani Y, et al: Usefulness of immunohistochemistry for the detection of the BRAF V600E mutation in Japanese lung adenocarcinoma. Lung Cancer. 82:51–54. 2013. View Article : Google Scholar : PubMed/NCBI

18 

Didelot A, Le Corre D, Luscan A, et al: Competitive allele specific TaqMan PCR for KRAS, BRAF and EGFR mutation detection in clinical formalin fixed paraffin embedded samples. Exp Mol Pathol. 92:275–280. 2012. View Article : Google Scholar : PubMed/NCBI

19 

Endo K, Sasaki H, Yano M, et al: Evaluation of the epidermal growth factor receptor gene mutation and copy number in non-small cell lung cancer with gefitinib therapy. Oncol Rep. 16:533–541. 2006.PubMed/NCBI

20 

Sasaki H, Okuda K, Kawano O, et al: Nras and Kras mutation in Japanese lung cancer patients: Genotyping analysis using LightCycler. Oncol Rep. 18:623–628. 2007.PubMed/NCBI

21 

Yokota K, Sasaki H, Okuda K, et al: KIF5B/RET fusion gene in surgically-treated adenocarcinoma of the lung. Oncol Rep. 28:1187–1192. 2012.PubMed/NCBI

22 

Shimuzu S, Yatabe Y, Koshikawa T, et al: High frequency of clonally related tumors in cases of multiple synchronous lung cancers as revealed by molecular diagnosis. Clin Cancer Res. 6:3994–3999. 2000.PubMed/NCBI

23 

Fidler IJ and Kripke ML: Metastasis results from preexisting variant cells within a malignant tumor. Science. 197:893–895. 1977. View Article : Google Scholar : PubMed/NCBI

24 

Navin N, Kendall J, Troge J, et al: Tumour evolution inferred by single-cell sequencing. Nature. 472:90–94. 2011. View Article : Google Scholar : PubMed/NCBI

25 

Katona TM, Jones TD, Wang M, et al: Genetically heterogeneous and clonally unrelated metastases may arise in patients with cutaneous melanoma. Am J Surg Pathol. 31:1029–1037. 2007. View Article : Google Scholar : PubMed/NCBI

26 

Ligel B, Kepten I, Le C, et al: Heterogeneity of kinase inhibitor resistance mechanisms in GIST. J Pathol. 216:64–74. 2008. View Article : Google Scholar : PubMed/NCBI

27 

Taniguchi K, Okami J, Kodama K, et al: Intratumor heterogeneity of epidermal growth factor receptor mutations in lung cancer and its correlation to the response to gefitinib. Cancer Sci. 99:929–935. 2008. View Article : Google Scholar : PubMed/NCBI

28 

Cardarella S, Oritz TM, Joshi VA, et al: The introduction of systematic genomic testing for patients with non-small-cell lung cancer. J Thorac Oncol. 7:1767–1774. 2012. View Article : Google Scholar : PubMed/NCBI

29 

Fecher LA, Amaravadi RK and Flaherty KT: The MAPK pathway in melanoma. Curr Opin Oncol. 20:183–189. 2008. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Tatematsu T, Sasaki H, Shimizu S, Hikosaka Y, Okuda K, Haneda H, Moriyama S, Yano M and Fujii Y: Intra‑tumor heterogeneity of BRAF V600E mutation in lung adenocarcinomas. Exp Ther Med 9: 1719-1722, 2015.
APA
Tatematsu, T., Sasaki, H., Shimizu, S., Hikosaka, Y., Okuda, K., Haneda, H. ... Fujii, Y. (2015). Intra‑tumor heterogeneity of BRAF V600E mutation in lung adenocarcinomas. Experimental and Therapeutic Medicine, 9, 1719-1722. https://doi.org/10.3892/etm.2015.2298
MLA
Tatematsu, T., Sasaki, H., Shimizu, S., Hikosaka, Y., Okuda, K., Haneda, H., Moriyama, S., Yano, M., Fujii, Y."Intra‑tumor heterogeneity of BRAF V600E mutation in lung adenocarcinomas". Experimental and Therapeutic Medicine 9.5 (2015): 1719-1722.
Chicago
Tatematsu, T., Sasaki, H., Shimizu, S., Hikosaka, Y., Okuda, K., Haneda, H., Moriyama, S., Yano, M., Fujii, Y."Intra‑tumor heterogeneity of BRAF V600E mutation in lung adenocarcinomas". Experimental and Therapeutic Medicine 9, no. 5 (2015): 1719-1722. https://doi.org/10.3892/etm.2015.2298
Copy and paste a formatted citation
x
Spandidos Publications style
Tatematsu T, Sasaki H, Shimizu S, Hikosaka Y, Okuda K, Haneda H, Moriyama S, Yano M and Fujii Y: Intra‑tumor heterogeneity of BRAF V600E mutation in lung adenocarcinomas. Exp Ther Med 9: 1719-1722, 2015.
APA
Tatematsu, T., Sasaki, H., Shimizu, S., Hikosaka, Y., Okuda, K., Haneda, H. ... Fujii, Y. (2015). Intra‑tumor heterogeneity of BRAF V600E mutation in lung adenocarcinomas. Experimental and Therapeutic Medicine, 9, 1719-1722. https://doi.org/10.3892/etm.2015.2298
MLA
Tatematsu, T., Sasaki, H., Shimizu, S., Hikosaka, Y., Okuda, K., Haneda, H., Moriyama, S., Yano, M., Fujii, Y."Intra‑tumor heterogeneity of BRAF V600E mutation in lung adenocarcinomas". Experimental and Therapeutic Medicine 9.5 (2015): 1719-1722.
Chicago
Tatematsu, T., Sasaki, H., Shimizu, S., Hikosaka, Y., Okuda, K., Haneda, H., Moriyama, S., Yano, M., Fujii, Y."Intra‑tumor heterogeneity of BRAF V600E mutation in lung adenocarcinomas". Experimental and Therapeutic Medicine 9, no. 5 (2015): 1719-1722. https://doi.org/10.3892/etm.2015.2298
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