SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)

These data provide an expanded understanding of the molecular underpinnings of EMCG-including the first description of a SMARCA4 frameshift variant in this entity-and demonstrate that while gastrointestinal marker immunoexpression is relatively common among endometrial carcinomas, strictly defined EMCG remains rare (<1%). As awareness of this entity grows, pathologists should take care not to over-interpret gastrointestinal marker expression as stand-alone evidence of an EMCG diagnosis.

In a clonogenic analysis either SMARCA4 or SMARCAD1 is required for cell survival. The SMARCA4-SMARCAD1 axis is a novel mechanism that provides tolerance for replication stress.

P2, N=6, Terminated, Prelude Therapeutics | Trial completion date: Dec 2027 --> Jan 2026 | Active, not recruiting --> Terminated | Trial primary completion date: Aug 2027 --> Jan 2026; Sponsor decision

This study is limited due to a small cohort and limited available clinical data. Larger cohort studies and prospective clinical trials are necessary to validate and explore the interplay between molecular and immune biomarkers as well as general biological mechanism in paving therapeutic way in melanoma.

SMARCA4 mutations conferred a poorer response for EGFR-mutant LUAD subgroups who received EGFR-TKIs. Additionally, chemotherapy plus anti-angiogenesis as first-line therapy may be more effective for Stage IV-SMARCA4 mutant LUAD with EGFR wt.

Frequent synaptophysin expression in SMARCA4-deficient UC of the oesophagus can lead to diagnostic confusion with neuroendocrine carcinomas, resulting in potential mismanagement. BRG1 IHC should be incorporated in the diagnostic workup of poorly differentiated oesophageal tumours to ensure accurate classification and guide effective treatment strategies.

He was treated with nine cycles of VDC-IE(vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide) chemotherapy given at 3-week intervals, complicated by transient iron deficiency anaemia, followed by surgical excision with neck dissection and fibular flap reconstruction. Maintenance therapy with the histone deacetylase inhibitor vorinostat was initiated. This case highlights the importance of early recognition, multimodal therapy and emerging targeted treatment in improving outcomes for NUT carcinoma.

Immunotherapy and targeted therapies show promise in managing thoracic SMARCA4-UT, warranting further investigation. Further exploring the genetic and molecular landscape of this tumor might reveal potential therapeutic targets.

Although eye development anomalies have occasionally been reported in individuals with a pathogenic variant in SMARCA4, no clear association has been established to date. The description of these three new individuals provides further evidence supporting the role of SMARCA4 in eye development and its likely involvement in structural eye malformations.

Non-viral c-JUN+B7-H3 CAR T cells show enhanced killing of both SCLC cells with low antigen density and thoracic SMARCA4-deficient UTs, providing a platform to address these highly aggressive entities. We also provide evidence that good manufacturing practice (GMP) clinical-scale manufacturing is feasible for c-JUN+B7-H3 CAR T cells.

Methylation analysis, in which tumors were compared with a control group of 68 SNF/SWI-deficient neoplasms and 18 cutaneous squamous cell carcinomas, revealed that primary cutaneous SMARCA4-deficient and SMARCB1-deficient neoplasms, along with SMARCA4-deficient carcinomas of other organs, constitute a unique group of neoplasms, distinct from other analyzed tumor entities. These results support the theory that these primary cutaneous SWI/SNF-deficient tumors represent a distinctive group of morphologically undifferentiated cutaneous carcinoma.