Recurrent PAX3-MAML3 fusion in biphenotypic sinonasal sarcoma

Abstract

Biphenotypic sinonasal sarcoma (SNS) is a newly described tumor of the nasal and paranasal areas. Herein, we report the novel recurring chromosomal translocation t(2;4)(q35;q31.1) in SNS. The translocation results in the formation of the fusion protein PAX3-MAML3, which is a potent transcriptional activator of PAX3 response elements. The SNS phenotype is characterized by aberrant expression of genes involved in neuroectodermal and myogenic differentiation, which closely simulates the developmental roles of PAX3.

Mastermind-Like 3 Controls Proliferation and Differentiation in Neuroblastoma

“…MAML3 forms a fusion protein with PAX3 in biphenotypic sinonasal sarcoma. This PAX3-MAML3 fusion protein is a potent transcriptional activator of PAX3 response elements (35). MAML2 is well documented to form a fusion protein with CRTC1 following a t(11;19) translocation, aberrantly activating cAMP/CREB signaling (36)(37)(38).…”

Newly Described Tumor Entities in Sinonasal Tract Pathology

“…Almost all examples of BSNS harbor rearrangements of PAX3, and the most frequent translocation partner is MAML3. PAX3-MAML3 appears to be specific for BSNS [50]. Huang et al [51] recently described a subset of BSNS cases with the same PAX3-NCOA1 fusions that can be seen in alveolar rhabdomyosarcoma.…”

“…Given the focal cytokeratin immunostaining and uniform nuclear features, a monophasic synovial sarcoma is another diagnostic consideration. However, all cases of BSNS have been negative for synovial sarcoma fusion transcripts [49,50]. Finally, the staghorn vasculature raises the possibility of glomangiopericytoma or solitary fibrous tumor.…”

“…The same group subsequently renamed the entity biphenotypic sinonasal sarcoma (BSNS) [50]. Thirty-six cases of BSNS have been reported [49][50][51][52]. They typically arise in the superior aspects of the nasal cavity and ethmoid sinuses of women (M:F ratio is 1:3) ranging in age from 24 to 85 (mean 52).…”

“…Almost half of patients with BSNS have experienced local recurrences, but none of the tumors have metastasized, and none of the patients have died of their disease [49,50].…”