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
Medicine International
Join Editorial Board Propose a Special Issue
Print ISSN: 2754-3242 Online ISSN: 2754-1304
Journal Cover
March-April 2024 Volume 4 Issue 2

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
March-April 2024 Volume 4 Issue 2

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 Open Access

Clinical genomic profiling of malignant giant cell tumor of bone: A retrospective analysis using a real‑world database

  • Authors:
    • Yusuke Tsuda
    • Koichi Okajima
    • Yuki Ishibashi
    • Liuzhe Zhang
    • Toshihide Hirai
    • Hidenori Kage
    • Aya Shinozaki-Ushiku
    • Katsutoshi Oda
    • Sakae Tanaka
    • Hiroshi Kobayashi
  • View Affiliations / Copyright

    Affiliations: Department of Orthopedic Surgery, The University of Tokyo Hospital, Tokyo 113-8655, Japan, Next-Generation Precision Medicine Development Laboratory, The University of Tokyo Hospital, Tokyo 113-8655, Japan, Division of Integrative Genomics, The University of Tokyo, Tokyo 113-8655, Japan
    Copyright: © Tsuda et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].
  • Article Number: 17
    |
    Published online on: February 22, 2024
       https://doi.org/10.3892/mi.2024.141
  • 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

Malignant giant cell tumor of bone (GCTB) is identified by the presence of multinucleated giant cells, with an aggressive behavior and a high risk of metastasis, which has not been genetically characterized in detail. H3 histone family member 3A (H3F3A) gene mutations are highly recurrent and specific in GCTB. The present study analyzed the clinical information and genomic sequencing data of eight cases of malignant GCTB (out of 384 bone sarcoma samples) using an anonymized genomic database. There were 5 males and 3 females among the cases, with a median age of 33 years at the time of the initial diagnosis. H3F3A G34W and G34L mutations were detected in 3 patients and 1 patient, respectively. In 75% of cases without H3F3A mutation, mitogen‑activated protein kinase (MAPK) signaling pathway gene alterations were found (KRAS single nucleotide variant, KRAS amplification, nuclear respiratory factor 1‑BRAF fusion). Moreover, the collagen type I alpha 2 chain‑ALK fusion was detected in remaining one case. The most frequent gene alterations were related to cell cycle regulators, including TP53, RB1, cyclin‑dependent kinase inhibitor 2A/B and cyclin E1 (75%, 6 of 8 cases). On the whole, the present study discovered recurrent MAPK signaling gene alterations or other gene alterations in cases of malignant GCTB. Of note, two fusion genes should be carefully validated following the pathology re‑review by sarcoma pathologists. These two fusion genes may be detected in resembling tumors, which contain giant cells, apart from malignant GCTB. The real‑world data used herein provide a unique perspective on genomic alterations in clinicopathologically diagnosed malignant GCTB.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Flanagan AM, Larousserie F, O'Doneell PG and Yoshida A: Giant Cell Tumor of Bone. In: WHO Classification of Tumours Editorial Board. Soft tissue and bone tumours. 5th edition. International Agency for Research on Cancer, Lyon, 2020.

2 

Bertoni F, Bacchini P and Staals EL: Malignancy in giant cell tumor of bone. Cancer. 97:2520–2529. 2003.PubMed/NCBI View Article : Google Scholar

3 

Behjati S, Tarpey PS, Presneau N, Scheipl S, Pillay N, Van Loo P, Wedge DC, Cooke SL, Gundem G, Davies H, et al: Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone. Nat Genet. 45:1479–1482. 2013.PubMed/NCBI View Article : Google Scholar

4 

Cleven AH, Hocker S, Briaire-de Bruijn I, Szuhai K, Cleton-Jansen AM and Bovee JV: Mutation analysis of H3F3A and H3F3B as a diagnostic tool for giant cell tumor of bone and chondroblastoma. Am J Surg Pathol. 39:1576–1583. 2015.PubMed/NCBI View Article : Google Scholar

5 

Yoshida KI, Nakano Y, Honda-Kitahara M, Wakai S, Motoi T, Ogura K, Sano N, Shibata T, Okuma T, Iwata S, et al: Absence of H3F3A mutation in a subset of malignant giant cell tumor of bone. Mod Pathol. 32:1751–1761. 2019.PubMed/NCBI View Article : Google Scholar

6 

Khazaei S, Jay ND, Deshmukh S, Hendrikse LD, Jawhar W, Chen CCL, Mikael LG, Faury D, Marchione DM, Lanoix J, et al: H3.3 G34W promotes growth and impedes differentiation of Osteoblast-Like mesenchymal progenitors in giant cell tumor of bone. Cancer Discov. 10:1968–1987. 2020.PubMed/NCBI View Article : Google Scholar

7 

Amary F, Berisha F, Ye H, Gupta M, Gutteridge A, Baumhoer D, Gibbons R, Tirabosco R, O'Donnell P and Flanagan AM: H3F3A (Histone 3.3) G34W Immunohistochemistry: A reliable marker defining benign and malignant giant cell tumor of bone. Am J Surg Pathol. 41:1059–1068. 2017.PubMed/NCBI View Article : Google Scholar

8 

Donigian S, Whiteway SL, Hipp SJ, Lybeck D and Clark RO: Malignant giant cell tumor of bone with a KRAS G12V mutation. J Pediatr Hematol Oncol. 44:e268–e271. 2022.PubMed/NCBI View Article : Google Scholar

9 

Oda Y, Sakamoto A, Saito T, Matsuda S, Tanaka K, Iwamoto Y and Tsuneyoshi M: Secondary malignant giant-cell tumour of bone: Molecular abnormalities of p53 and H-ras gene correlated with malignant transformation. Histopathology. 39:629–637. 2001.PubMed/NCBI View Article : Google Scholar

10 

Fittall MW, Lyskjaer I, Ellery P, Lombard P, Ijaz J, Strobl AC, Oukrif D, Tarabichi M, Sill M, Koelsche C, et al: Drivers underpinning the malignant transformation of giant cell tumour of bone. J Pathol. 252:433–440. 2020.PubMed/NCBI View Article : Google Scholar

11 

Ishihara S, Yamamoto H, Iwasaki T, Toda Y, Yamamoto T, Yoshimoto M, Ito Y, Susuki Y, Kawaguchi K, Kinoshita I, et al: Histological and immunohistochemical features and genetic alterations in the malignant progression of giant cell tumor of bone: A possible association with TP53 mutation and loss of H3K27 trimethylation. Mod Pathol. 35:640–648. 2022.PubMed/NCBI View Article : Google Scholar

12 

Mukai Y and Ueno H: Establishment and implementation of cancer genomic medicine in Japan. Cancer Sci. 112:970–977. 2021.PubMed/NCBI View Article : Google Scholar

13 

Kohno T, Kato M, Kohsaka S, Sudo T, Tamai I, Shiraishi Y, Okuma Y, Ogasawara D, Suzuki T, Yoshida T and Mano H: C-CAT: The national datacenter for cancer genomic medicine in Japan. Cancer Discov. 12:2509–2515. 2022.PubMed/NCBI View Article : Google Scholar

14 

Riely GJ, Kris MG, Rosenbaum D, Marks J, Li A, Chitale DA, Nafa K, Riedel ER, Hsu M, Pao W, et al: Frequency and distinctive spectrum of KRAS mutations in never smokers with lung adenocarcinoma. Clin Cancer Res. 14:5731–5734. 2008.PubMed/NCBI View Article : Google Scholar

15 

Modest DP, Ricard I, Heinemann V, Hegewisch-Becker S, Schmiegel W, Porschen R, Stintzing S, Graeven U, Arnold D, von Weikersthal LF, et al: Outcome according to KRAS-, NRAS- and BRAF-mutation as well as KRAS mutation variants: pooled analysis of five randomized trials in metastatic colorectal cancer by the AIO colorectal cancer study group. Ann Oncol. 27:1746–1753. 2016.PubMed/NCBI View Article : Google Scholar

16 

Halbrook CJ, Lyssiotis CA, Pasca di Magliano M and Maitra A: Pancreatic cancer: Advances and challenges. Cell. 186:1729–1754. 2023.PubMed/NCBI View Article : Google Scholar

17 

Yang Y, Zhang H, Huang S and Chu Q: KRAS mutations in solid tumors: Characteristics, current therapeutic strategy, and potential treatment exploration. J Clin Med. 12(709)2023.PubMed/NCBI View Article : Google Scholar

18 

Lutsik P, Baude A, Mancarella D, Öz S, Kühn A, Toth R, Hey J, Toprak UH, Lim J, Nguyen VH, et al: Globally altered epigenetic landscape and delayed osteogenic differentiation in H3.3-G34W-mutant giant cell tumor of bone. Nat Commun. 11(5414)2020.PubMed/NCBI View Article : Google Scholar

19 

Phillips JJ, Gong H, Chen K, Joseph NM, van Ziffle J, Jin LW, Bastian BC, Bollen AW, Perry A, Nicolaides T, et al: Activating NRF1-BRAF and ATG7-RAF1 fusions in anaplastic pleomorphic xanthoastrocytoma without BRAF p.V600E mutation. Acta Neuropathol. 132:757–760. 2016.PubMed/NCBI View Article : Google Scholar

20 

Isaacson AL, Guseva NV, Bossler AD and Ma D: Urothelial carcinoma with an NRF1-BRAF rearrangement and response to targeted therapy. Cold Spring Harb Mol Case Stud. 5(a003848)2019.PubMed/NCBI View Article : Google Scholar

21 

Chang KTE, Tay AZE, Kuick CH, Chen H, Algar E, Taubenheim N, Campbell J, Mechinaud F, Campbell M, Super L, et al: ALK-positive histiocytosis: an expanded clinicopathologic spectrum and frequent presence of KIF5B-ALK fusion. Mod Pathol. 32:598–608. 2019.PubMed/NCBI View Article : Google Scholar

22 

Kashima J, Yoshida M, Jimbo K, Izutsu K, Ushiku T, Yonemori K and Yoshida A: ALK-positive histiocytosis of the breast: A clinicopathologic study highlighting spindle cell histology. Am J Surg Pathol. 45:347–355. 2021.PubMed/NCBI View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
Copy and paste a formatted citation
Spandidos Publications style
Tsuda Y, Okajima K, Ishibashi Y, Zhang L, Hirai T, Kage H, Shinozaki-Ushiku A, Oda K, Tanaka S, Kobayashi H, Kobayashi H, et al: Clinical genomic profiling of malignant giant cell tumor of bone: A retrospective analysis using a real‑world database. Med Int 4: 17, 2024.
APA
Tsuda, Y., Okajima, K., Ishibashi, Y., Zhang, L., Hirai, T., Kage, H. ... Kobayashi, H. (2024). Clinical genomic profiling of malignant giant cell tumor of bone: A retrospective analysis using a real‑world database. Medicine International, 4, 17. https://doi.org/10.3892/mi.2024.141
MLA
Tsuda, Y., Okajima, K., Ishibashi, Y., Zhang, L., Hirai, T., Kage, H., Shinozaki-Ushiku, A., Oda, K., Tanaka, S., Kobayashi, H."Clinical genomic profiling of malignant giant cell tumor of bone: A retrospective analysis using a real‑world database". Medicine International 4.2 (2024): 17.
Chicago
Tsuda, Y., Okajima, K., Ishibashi, Y., Zhang, L., Hirai, T., Kage, H., Shinozaki-Ushiku, A., Oda, K., Tanaka, S., Kobayashi, H."Clinical genomic profiling of malignant giant cell tumor of bone: A retrospective analysis using a real‑world database". Medicine International 4, no. 2 (2024): 17. https://doi.org/10.3892/mi.2024.141
Copy and paste a formatted citation
x
Spandidos Publications style
Tsuda Y, Okajima K, Ishibashi Y, Zhang L, Hirai T, Kage H, Shinozaki-Ushiku A, Oda K, Tanaka S, Kobayashi H, Kobayashi H, et al: Clinical genomic profiling of malignant giant cell tumor of bone: A retrospective analysis using a real‑world database. Med Int 4: 17, 2024.
APA
Tsuda, Y., Okajima, K., Ishibashi, Y., Zhang, L., Hirai, T., Kage, H. ... Kobayashi, H. (2024). Clinical genomic profiling of malignant giant cell tumor of bone: A retrospective analysis using a real‑world database. Medicine International, 4, 17. https://doi.org/10.3892/mi.2024.141
MLA
Tsuda, Y., Okajima, K., Ishibashi, Y., Zhang, L., Hirai, T., Kage, H., Shinozaki-Ushiku, A., Oda, K., Tanaka, S., Kobayashi, H."Clinical genomic profiling of malignant giant cell tumor of bone: A retrospective analysis using a real‑world database". Medicine International 4.2 (2024): 17.
Chicago
Tsuda, Y., Okajima, K., Ishibashi, Y., Zhang, L., Hirai, T., Kage, H., Shinozaki-Ushiku, A., Oda, K., Tanaka, S., Kobayashi, H."Clinical genomic profiling of malignant giant cell tumor of bone: A retrospective analysis using a real‑world database". Medicine International 4, no. 2 (2024): 17. https://doi.org/10.3892/mi.2024.141
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