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Genomic Profiling of the Craniofacial Ossifying Fibroma by Next-Generation Sequencing

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Abstract

Background

Ossifying fibroma (OF) of the craniofacial skeleton is a fibro-osseous lesion characterized by various patterns of bone formation in a cellular fibroblastic stroma. The molecular landscape of OF remains mostly unknown. There are a few known pathogenic abnormalities in OF, including HRPT2 mutations in conventional OF and SATB2 translocations in juvenile psammomatoid OF. On the other hand, conflicting reports exist regarding MDM2 gene amplification and chromosomal copy number alterations (CNA) in OF.

Methods

Surgically removed biopsies and curettage specimens from OF patients were obtained. Clinical, radiographic, and pathologic features of tumors were reviewed. Genomic DNA was extracted from formalin-fixed, paraffin-embedded blocks of tumor tissue. Capture-based DNA next-generation sequencing targeting the coding regions 529 cancer genes and select introns was performed.

Results

We identified 17 OF cases from 8 male and 8 female patients with mean age of 22 years (range 1–58 years). Nine case occurred in the gnathic bones and 8 in the extragnathic craniofacial bones. These cases included 3 juvenile psammomatoid OF, 6 conventional OF and 8 juvenile trabecular OF. Large-scale CNAs were present in 6 of 17 cases. Seven cases (41%) had focal amplifications including FOSB (n = 2, 11%), FOS (n = 4, 23%), COL1A1 (n = 4, 23%) and TBX3 (n = 5, 29%). Three cases (17%) had pathogenic CDC73 mutations. No cases showed focal MDM2 amplification.

Conclusions

Here, we provided a comprehensive molecular characterization of OF that reveals a heterogeneous genetic profile with occasional large-scale CNAs (n = 6, 35%). FOS, FOSB, and TBX3 genes that regulate AP-1 transcriptional complex are frequently altered in OF (n = 7, 41%), chiefly in juvenile trabecular OF. These genes encode transcription factors that act as downstream effectors of the MAP kinase signaling pathway. MDM2 amplification is an exceedingly rare event in OF, if present at all, so identification of this event should continue to raise concern for low-grade gnathic osteosarcoma. In summary, our findings suggest that OF represents a heterogeneous group of tumors at the genetic level but dysregulation of the AP-1 pathway may play a role in pathogenesis of juvenile trabecular OF.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Code Availability

Not applicable.

Disclosures

Data from this manuscript was presented, in part, at the annual meeting of United States and Canadian Academy of Pathology, with an embargo on publication until its completion, March 16, 2023.

The full research will be published in Head and Neck Pathology.

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Funding

The study was funded by the University California at San Francisco Department of Pathology, Clinical Research Endowment.

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Authors and Affiliations

  1. Department of Pathology, University of California at San Francisco, San Francisco, CA, 94143, USA

    Dorukhan H. Bahceci, James P. Grenert & Richard C. K. Jordan

  2. Department of Pathology, University of California at San Francisco, 1825 4Th Street, Room M2354, San Francisco, CA, 94158, USA

    Andrew E. Horvai

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All authors confirm they have meaningfully contributed to the research and read and approved the final manuscript. Data from this manuscript was presented, in part, at the annual meeting of United States and Canadian Academy of Pathology, with an embargo on publication until its completion, March 16, 2023.The full research will be published in Head and Neck Pathology.

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Correspondence to Andrew E. Horvai.

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This study has obtained IRB approval the Institutional Review Board at the University of California, San Francisco (IRB#11-05361). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Bahceci, D.H., Grenert, J.P., Jordan, R.C.K. et al. Genomic Profiling of the Craniofacial Ossifying Fibroma by Next-Generation Sequencing. Head and Neck Pathol 17, 722–730 (2023). https://doi.org/10.1007/s12105-022-01523-9

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