PMID- 38476985
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240314
IS  - 2754-1304 (Electronic)
IS  - 2754-3242 (Print)
IS  - 2754-1304 (Linking)
VI  - 4
IP  - 2
DP  - 2024 Mar-Apr
TI  - Clinical genomic profiling of malignant giant cell tumor of bone: A retrospective 
      analysis using a real‑world database.
PG  - 17
LID - 10.3892/mi.2024.141 [doi]
LID - 17
AB  - 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.
CI  - Copyright: (c) 2024 Tsuda et al.
FAU - Tsuda, Yusuke
AU  - Tsuda Y
AD  - Department of Orthopedic Surgery, The University of Tokyo Hospital, Tokyo 
      113-8655, Japan.
AD  - Department of Oral and Maxillofacial Surgery, The University of Tokyo Hospital, 
      Tokyo 113-8655, Japan.
FAU - Okajima, Koichi
AU  - Okajima K
AD  - Department of Orthopedic Surgery, The University of Tokyo Hospital, Tokyo 
      113-8655, Japan.
FAU - Ishibashi, Yuki
AU  - Ishibashi Y
AD  - Department of Orthopedic Surgery, The University of Tokyo Hospital, Tokyo 
      113-8655, Japan.
FAU - Zhang, Liuzhe
AU  - Zhang L
AD  - Department of Orthopedic Surgery, The University of Tokyo Hospital, Tokyo 
      113-8655, Japan.
FAU - Hirai, Toshihide
AU  - Hirai T
AD  - Department of Orthopedic Surgery, The University of Tokyo Hospital, Tokyo 
      113-8655, Japan.
FAU - Kage, Hidenori
AU  - Kage H
AD  - Next-Generation Precision Medicine Development Laboratory, The University of 
      Tokyo Hospital, Tokyo 113-8655, Japan.
AD  - Department of Respiratory Medicine, The University of Tokyo Hospital, Tokyo 
      113-8655, Japan.
FAU - Shinozaki-Ushiku, Aya
AU  - Shinozaki-Ushiku A
AD  - Division of Integrative Genomics, The University of Tokyo, Tokyo 113-8655, Japan.
FAU - Oda, Katsutoshi
AU  - Oda K
AD  - Division of Integrative Genomics, The University of Tokyo, Tokyo 113-8655, Japan.
AD  - Department of Gynecology, The University of Tokyo Hospital, Tokyo 113-8655, 
      Japan.
FAU - Tanaka, Sakae
AU  - Tanaka S
AD  - Department of Orthopedic Surgery, The University of Tokyo Hospital, Tokyo 
      113-8655, Japan.
FAU - Kobayashi, Hiroshi
AU  - Kobayashi H
AD  - Department of Orthopedic Surgery, The University of Tokyo Hospital, Tokyo 
      113-8655, Japan.
LA  - eng
PT  - Journal Article
DEP - 20240222
PL  - England
TA  - Med Int (Lond)
JT  - Medicine international
JID - 9918383867606676
PMC - PMC10928650
OTO - NOTNLM
OT  - MAPK signaling
OT  - genome
OT  - malignant giant cell tumor of bone
OT  - sarcoma
COIS- The authors declare that they have no competing interests.
EDAT- 2024/03/13 06:46
MHDA- 2024/03/13 06:47
PMCR- 2024/02/22
CRDT- 2024/03/13 04:01
PHST- 2023/09/29 00:00 [received]
PHST- 2024/02/13 00:00 [accepted]
PHST- 2024/03/13 06:47 [medline]
PHST- 2024/03/13 06:46 [pubmed]
PHST- 2024/03/13 04:01 [entrez]
PHST- 2024/02/22 00:00 [pmc-release]
AID - MI-4-2-00141 [pii]
AID - 10.3892/mi.2024.141 [doi]
PST - epublish
SO  - Med Int (Lond). 2024 Feb 22;4(2):17. doi: 10.3892/mi.2024.141. eCollection 2024 
      Mar-Apr.