ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2015
Chromosome 12 long arm rearrangement covering MDM2 and RASAL1 is associated with aggressive craniofacial juvenile ossifying fibroma and extracranial psammomatoid fibro-osseous lesions.
Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumors: Odontogenic and Maxillofacial Bone Tumours.Head and neck pathology · 2022Pooled it
- Molecular Alterations in Osteosarcomas of the Oral and Maxillofacial Region: A Scoping Review.Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology · 2026Article
- Benign fibro-osseous lesions of the cranio-maxillofacial bones: an updated review with special emphasis on molecular pathogenesis.Journal of bone and mineral metabolism · 2026Review
- Aggressive Juvenile Trabecular Ossifying Fibroma in a 4-Year-Old: Case Report Bringing Diagnostic Challenges and Surgical Management.Case reports in dentistry · 2026Article
- [A case report and literature review of juvenile trabecular ossifying fibroma originating from the uncinate process].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2025Review
- Primary osseous tumors of the orbit.Virchows Archiv : an international journal of pathology · 2025Review
- Assessment of MDM2 Gene Locus Amplification by Fluorescence In-Situ Hybridization in Juvenile Ossifying Fibroma.Head and neck pathology · 2024Article
- Immunohistochemical analysis of osteoclastic and osteoblastic activity in ossifying fibroma and juvenile ossifying fibroma: A comparative study.Journal of medicine and life · 2023Article
- Genomic Profiling of the Craniofacial Ossifying Fibroma by Next-Generation Sequencing.Head and neck pathology · 2023Article
- [The new WHO classification of jaw tumours].Pathologie (Heidelberg, Germany) · 2023Review
- Cemento-Osseous Dysplasia of the Jaw: Demographic and Clinical Analysis of 191 New Cases.Dentistry journal · 2023Article
- MDM2 Gene Amplification and Expression of MDM2 and CDK4 are Rare in Ossifying Fibroma of Craniofacial Bones.Head and neck pathology · 2022Article
- Ossifying Fibromas of the Head and Neck Region: A Clinicopathological Study of 45 Cases.Head and neck pathology · 2022Article
- Juvenile trabecular ossifying fibroma: Immunohistochemical expression of MDM2, CDK4 and p53 compared to conventional ossifying fibroma.Journal of clinical and experimental dentistry · 2022Article
- SATB2 and MDM2 Immunoexpression and Diagnostic Role in Primary Osteosarcomas of the Jaw.Dentistry journal · 2021Article
- First presentation of a frameshift mutation in the SETD2 gene of a juvenile psammomatoid ossifying fibroma (JPOF) associated with an aneurysmal bone cyst.Diagnostic pathology · 2021Article
- Juvenile psammomatoid ossifying fibroma of the parietal bone and review of calvarial presentations: illustrative case.Journal of neurosurgery. Case lessons · 2021Article
- Copy number alteration profiling facilitates differential diagnosis between ossifying fibroma and fibrous dysplasia of the jaws.International journal of oral science · 2021Article
- Juvenile trabecular ossifying fibroma of the maxilla: Case report of a diagnostic dilemma.Dental research journal · 2021Article
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8 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To evaluate the diagnostic value of MDM2 status in craniofacial fibro-osseous lesions, we investigated MDM2 expression by immunohistochemistry and analyzed MDM2 amplification by qPCR in 30 cases of ossifying fibroma (including 13 cases of the juvenile variant) and 17 cases of fibrous dysplasia. Two cases of uncommon extragnathic psammomatoid fibrous dysplasia and a mixed control group of 15 cases of low-grade osteosarcoma and 15 cases of well-differentiated/dedifferentiated liposarcoma were included. MDM2 amplification was found in 33% of ossifying fibromas (peak of 69% for the juvenile variant) and in 12% of fibrous dysplasia, in none of which was MDM2 overexpressed. All control cases exhibited MDM2 amplification and overexpression. To investigate possible polysomy of chromosome 12, we studied RASAL1 amplification, a gene telomeric to MDM2 on the long arm of chromosome 12. RASAL1 amplification was reported in all benign fibro-osseous lesions exhibiting MDM2 amplification but not in controls. Simultaneous amplification of these two genes was significantly higher in juvenile ossifying fibromas compared with fibrous dysplasia (P=0.004), non-juvenile ossifying fibromas (P=0.001), and all other benign craniofacial fibro-osseous lesions combined (P=0.0001). Of the nine cases of juvenile ossifying fibroma exhibiting amplification, three were locally invasive and four were recurrent, suggesting aggressive disease. The two cases of extragnathic psammomatoid fibrous dysplasia also showed MDM2 and RASAL1 amplification with no MDM2 overexpression. This large chromosome 12 rearrangement, spanning MDM2 and RASAL1, is the first recurrent molecular abnormality to be reported in juvenile ossifying fibroma. It may represent both a molecular diagnostic marker and a characteristic of more aggressive forms with a higher risk of recurrence. Finally, the presence of this rearrangement in extragnathic psammomatoid fibro-osseous lesions mimicking ossifying fibromas might reflect a common molecular pathway in their pathogenesis and calls into question the classification of such lesions within fibrous dysplasia.
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