NCOR2 (Nuclear Receptor Corepressor 2)

Using murine mammary organoids, we mapped estrogen (E2) and progesterone (P4) responses at single-cell resolution...MCF7 cells show delayed activation kinetics and reach a lower response plateau. Together, these findings reveal that hormone response magnitude varies independently of receptor abundance in mammary organoids and follows distinct activation dynamics in human ERα + cancer cells.

Recent examples include spindle cell rhabdomyosarcomas with TFCP2 fusions, keratin-positive giant-cell rich tumors with HMGA2::NCOR2 fusions, NR1D1- rearranged sarcomas, malignant epithelioid neoplasms with FET::CREB fusions, and the very recently described ossifying spindled and epithelioid tumors (OSET). This review will address the unique clinical, histologic, and immunophenotypic characteristics of these rare neoplasms and provide practical considerations for molecular testing in challenging cases of keratin-positive mesenchymal neoplasia.

This case expands the clinical spectrum of pediatric KPGCT and suggests that imatinib may be an effective treatment option in infants with advanced disease, even canonical HMGA2::NCOR2 fusion absent.

CONCLUSIONS Our findings suggest multi-omic switch-like regulation may underlie differential COPD/IPF etiology. Future investigation of LPCAT1 and ATP11A could provide new mechanistic understanding and therapeutic avenues.

Furthermore, we retrieved single-cell sequencing datasets for tumors from cancer patients and found that unbiased signatures identified here through proteomic analysis were able to separate proinflammatory macrophage populations in a clinical setting and could thus be used to expand state-specific markers. This study contributes to in-depth multi-omics characterizations of macrophage phenotypic landscapes, which could be valuable for assisting future interventions that therapeutically alter immune cell compartments.

The X-ray crystal structure of 4 bound to the BTB (Broad-Complex, Tramtrack, and Bric à brac) domain of BCL6 revealed a large back pocket as well as a left-hand channel adjacent to the ligand that could be leveraged to optimize these compounds. Sulfonamide side chains were therefore introduced to target this space, leading to compounds 11d and 11e having sub-micromolar binding to the BTB domain of BCL6.

Sampling revealed a HMGA2::NCOR2 fusion associated with a recently described subset of giant cell-rich bone and soft tissue tumors. This case expands the differential diagnosis for cross-physeal and epiphyseal bone tumors in pediatric patients and highlights the radiological features of keratin-positive giant cell-rich tumor (KPGCT).

The possibility of molecular glioblastoma should be considered for these tumors. It is thus recommended to perform genetic testing on diffuse gliomas with PLNTY features in order to facilitate integrated diagnosis and provide molecular evidence for accurate evaluation of prognoses.

This case expands the understanding of GLI1-altered mesenchymal tumours, especially in uncommon sites like the pleura, and highlights the importance of multidisciplinary decision-making. Ongoing molecular and pathological analysis is critical to establish robust diagnostic and prognostic frameworks for such rare tumour entities.

Genomic alterations and reduced TIL density underpin trastuzumab resistance. The novel TRAG signature and integrated prognostic model enhance risk stratification and may guide personalized adjuvant therapy in early-stage HER2+ BC.

This study investigates how BQ overexpression drives doxorubicin (DOX) resistance by enhancing androgen receptor (AR) signaling and non-homologous end joining (NHEJ)...AR inhibition with bicalutamide in BQ overexpressing cells reversed DOX resistance...Cox-regression analysis showed that high CCRK was a poorer prognostic factor of overall survival (p < 0.001; RR 3.056, 95% CI 1.661, 5.621, AR (p < 0.001; RR 3.420, 95% CI 1.783, 6.562), and disease-specific survival (p < 0.001; RR 2.731, 95% CI 1.472, 5.067). The BQ-AR-CCRK-KU70 axis represents a novel mechanism of DOX resistance in ER+ve breast cancer, suggesting AR or CCRK inhibition as a potential therapeutic strategy.

Xanthogranulomatous epithelial tumor is a recently described neoplasm harboring recurrent HMGA2::NCOR2 fusions, which, owing to its extensive xanthogranulomatous appearance with abundant foamy histiocytes and frequent Touton-type giant cells, may be confused with other inflammatory and neoplastic entities. We present a case arising in the right arm subcutaneous tissues of a 10-year-old boy, which was initially interpreted as a non-Langerhans cell histiocytic neoplasm compatible with Juvenile xanthogranuloma.