Malignant chondroid syringoma is genetically related to tumors with PHF1 rearrangements such as low-grade endometrial sarcoma and ossifying fibromyxoid tumor, but also with tumors having TFE3 rearrangements such as renal cell carcinoma, alveolar soft part sarcoma, PEComa, and epithelioid hemangioendothelioma.
As a subset of OFMT still lack known genetic abnormalities, we identified two OFMTs negative forPHF1 and BCOR rearrangements, which were subjected to transcriptome analysis for fusion discovery.
It is now established that OFMTs represent translocation-associated tumors, with up to 85% associated with recurrent gene rearrangements, mostly involving the PHF1 gene (including in typical, atypical, and malignant neoplasms), with EP400-PHF1 in approximately 40% of tumors, and ZC3H7B-BCOR, MEAF6-PHF1, and EPC1-PHF1 fusions also described.
Thus, the PHF1 gene, previously shown to be the 3'-partner of fusion genes in endometrial stromal tumors, is also recurrently involved in the pathogenesis of OFMTs, irrespective of whether they are diagnosed as typical, atypical, or malignant lesions.