NCOA2 (Nuclear Receptor Coactivator 2)

Clinically, reduced SIRT6 expression coupled with elevated NCOA2 and mitochondrial/β-oxidation markers correlates with metastatic progression in bladder cancer. Together, these findings identify a previously unrecognized SIRT6-NCOA2-PPARα signaling axis as a metabolic vulnerability in bladder cancer.

MCS is a rare, high-grade sarcoma with limited treatment options. Targeted therapies against HEY1::NCOA2-associated pathways are promising and are currently under investigation.

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

The patient was treated with VAC chemotherapy (vincristine, actinomycin D, cyclophosphamide), local radiotherapy (60 Gy), cranial prophylactic radiotherapy (12 Gy), and subsequent debulking surgery. Multimodal treatment incorporating chemotherapy, radiotherapy, surgery, and targeted maintenance therapy can achieve meaningful disease control in aggressive craniofacial MCS. To our knowledge, this represents one of the very few reported pediatric cases of maxillary MCS with confirmed HEY1::NCOA2 fusion managed with sirolimus-based maintenance therapy.

At 20 months the patient is disease-free with regular menses and intact fertility. We review diagnostic clues, differential diagnoses, molecular taxonomy and fertility-sparing strategies, underscoring the value of comprehensive genomic profiling for accurate classification and prognostication of this uncommon uterine tumor.

Collectively, these findings suggest a multitarget biological and multipathway pharmacological profile for F. trinervia, consistent with previously reported biological activities. The concordance between in silico predictions and existing experimental evidence strengthens the pharmacological relevance of the identified metabolites and supports their prioritization for further experimental validation, including mechanistic and pharmacokinetic studies, in metabolic, immune, neurological, and cancer-related contexts.

This case highlights UTROSCT's aggressive potential in young patients and underscores the diagnostic utility of molecular testing (e.g., GREB1 rearrangements) to distinguish it from mimics like LG-ESS. The fatal outcome suggests GREB1-NCOA2 may correlate with high-risk behavior, warranting close follow-up.

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.