NCOA2 (Nuclear Receptor Coactivator 2)

No specific clustering was seen among different fusion types or tumor grade. Our findings support that BSS represents a unique and molecularly distinct sinonasal sarcoma with a characteristic DNA methylation signature, independent of gene fusion partners or histologic progression, providing a valuable tool for the classification of challenging cases.

This multicentre study confirms that anthracycline-based regimens show activity in MCS, with responses more in line with soft tissue sarcoma than Ewing sarcoma. Their benefit in localized disease remains uncertain, but (neo)adjuvant chemotherapy with Ewing-like regimens should be considered for patients eligible for surgery. In advanced disease, trabectedin may provide prolonged disease control after anthracyclines.

As we enter the era of precision medicine, classifying cancers by molecular markers will become increasingly valuable. Our investigation enriches the literature by identifying novel mutations and mutations exclusive to certain demographic groups. These findings support a shift beyond histology toward molecularly informed diagnostics and pathway-directed therapeutic hypotheses for MFS. Next steps should validate candidate markers in independent cohorts and link genomic profiles to clinicopathologic features, disease course, and treatment response to improve clinical translation. These observations will help shape diagnostics and targeted therapies against MFS.

This study expands the overlapping morphologic and molecular spectrum of uterine neoplasms resembling uAS showing recurrent fusions (mostly ESR1::NCOA3/2), associated with mostly low-grade histology, lack of heterologous elements and paucity of stromal overgrowth. The nosological relationship of these uAS-like tumors to UTROSCT (driven similarly by ESR1::NCOA3/2 fusions) and to fusion-negative high-grade uAS remains to be verified in future studies utilizing epigenetics and other tools.

As the first known case to date with this fusion, these findings contribute to the emerging research on genomic testing in acral soft tissue tumors. Additional cases and longer clinical follow-up are needed to better characterize the novel HMGA2::NCOA2 fusion.

Overall, our findings confirm that GREB1-rearranged uterine tumours are part of the UTROSCT spectrum, though they frequently exhibit a more diffuse growth pattern and a higher degree of genomic instability.

These genetic alterations were conspicuously absent in primary tumors, suggesting their potential role in metastatic progression. Our findings represent the first demonstration of CNV-driven oncogenic evolution in UTROSCTs, particularly implicating SWI/SNF complex dysregulation in metastatic competence.

Trabectedin demonstrates low disease control rate in translocation-related sarcomas, including few MCS cases. Anti-angiogenic tyrosine kinase inhibitors, such as apatinib and pazopanib, demonstrate activity in chondrosarcoma, but MCS-specific data are lacking. IDH1 inhibition benefits conventional subtypes rather than MCS. Early immunotherapy experience is limited, but pathway-directed strategies targeting BCL2 and PI3K-mTOR warrant evaluation.

In conclusion, ZFTA::NCOA1/2-rearranged epithelioid mesenchymal tumors represent a novel, morphologically distinct entity, genetically and epigenetically overlapping with chondroid lipoma. Expanded cohorts and long-term follow-up are necessary to clarify their precise classification and biologic behavior.

P2, N=16, Recruiting, Italian Sarcoma Group | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Aug 2025 --> Dec 2025

This was the first study to evaluate the performance of whole RNA-seq in fusion detection in patients with acute leukemia in Korea. Incorporating RNA-seq into diagnostic workflows may facilitate earlier and more precise therapeutic decisions and improve prognostic assessment in patients with acute leukemia.