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

  • Published online on: February 22, 2024     https://doi.org/10.3892/mi.2024.141
  • Article Number: 17
  • Copyright : © Tsuda et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

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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.
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March-April 2024
Volume 4 Issue 2

Print ISSN: 2754-3242
Online ISSN:2754-1304

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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