Biphenotypic sinonasal sarcoma diagnosed by detection of PAX3-MAML3 fusion gene using integrated whole-genome and transcriptome sequencing

Int Cancer Conf J. 2024 Jul 10;13(4):412-421. doi: 10.1007/s13691-024-00703-4. eCollection 2024 Oct.

Abstract

Biphenotypic sinonasal sarcoma (BSNS) is a double-phenotype sarcoma that shows differentiation in both the nervous and muscular systems. To date, whole-genome and transcriptome sequencing (WGTS) has not been used to analyze BSNS. We report a patient with BSNS who was diagnosed based on PAX3 rearrangement using WGTS. A 71-year-old Japanese male without remarkable symptoms showed a nasal tumor when undergoing computed tomography. Although pathological examination revealed a non-characteristic spindle cell tumor, a definitive diagnosis could not be made based on this examination. Endoscopic sinus surgery was performed for subsequent diagnosis, treatment, and WGTS. WGTS revealed a t(2; 4)(q35; q31.1) reciprocal translocation, resulting in a PAX3-MAML3 fusion gene, leading to a definitive diagnosis of BSNS. We also detected upregulation of the expression of PAX3, MAML3, and 11 known genes involved in neural and myogenic differentiation relevant to the BSNS phenotype. Hence, using WGTS in combination with conventional pathological diagnosis can contribute to a definitive diagnosis of rare cancers, including BSNS, by detecting chromosomal rearrangements or diagnostic markers.

Keywords: Gene Fusion; Noso neoplasm; RNA sequencing; Sarcoma; Whole genome sequencing.