Parafibromin Abnormalities in Ossifying Fibroma

Area of Science:

• Oncology
• Genetics
• Pathology

Background:

• Ossifying fibromas are rare tumors.
• Hyperparathyroidism-jaw tumor syndrome (HPT-JT) involves HRPT2/CDC73 gene mutations.
• CDC73 mutations and parafibromin protein loss are implicated in HPT-JT.

Purpose of the Study:

• To investigate the role of parafibromin loss in sporadic ossifying fibromas.
• To determine if parafibromin downregulation is common in non-syndromic ossifying fibroma.

Main Methods:

• Immunohistochemistry used to assess parafibromin protein expression in 9 ossifying fibromas.
• CDC73 gene sequencing (Sanger and AmpliSeq) performed on tumor samples.

Main Results:

• Four out of nine ossifying fibromas exhibited complete loss of nuclear parafibromin.
• Aberrant cytoplasmic parafibromin expression was noted in one case.
• CDC73 mutations were identified in two cases with abnormal parafibromin expression.

Conclusions:

• Loss of parafibromin protein expression may contribute to the pathogenesis of a subset of ossifying fibromas.
• Provides evidence for the involvement of the CDC73/parafibromin tumor suppressor in sporadic ossifying fibroma development.