Psammomatoid Ossifying Fibroma Is Defined by SATB2 Rearrangement

Area of Science:

• Oncology
• Genetics
• Pathology

Background:

• Psammomatoid ossifying fibroma (PsOF) is a benign fibro-osseous neoplasm with overlapping clinical and morphological features with other lesions.
• Accurate diagnosis of PsOF can be challenging, necessitating the identification of reliable molecular markers.

Purpose of the Study:

• To identify specific genes involved in chromosomal breakpoints in PsOF.
• To determine the frequency of SATB2 gene rearrangements in PsOF and differentiate it from other fibro-osseous lesions.

Main Methods:

• Whole RNA transcriptome sequencing was performed on PsOF tissue samples.
• Reverse transcription (RT)-PCR and fluorescence in situ hybridization (FISH) were used to validate gene fusions and rearrangements.
• SATB2 expression was analyzed using FISH and immunohistochemistry in PsOF, juvenile trabecular ossifying fibromas (JTOFs), and cemento-ossifying fibromas (COFs).

Main Results:

• A fusion transcript involving SATB2 and AL513487.1 was identified in one PsOF case.
• SATB2 gene rearrangements were found in 58% of evaluable PsOF cases but not in JTOF or COF cases.
• Tumor cells with SATB2 rearrangement showed reduced or absent SATB2 expression, contrasting with typical expression in JTOF and COF.

Conclusions:

• SATB2 rearrangement is a recurrent and highly specific molecular alteration in PsOF.
• This finding supports that PsOF is genetically distinct from JTOF and COF.
• The identification of SATB2 rearrangement aids in the accurate diagnosis and classification of PsOF.