ARID1A mutation

P2, N=84, Recruiting, National Cancer Institute, Naples

Furthermore, patient-derived organoids from ARID1A-low human tumors exhibited heightened RSL-3 sensitivity rather than ARID1A-high tumor. Our findings establish ferroptosis as a targetable vulnerability in ARID1A-deficient bladder cancer and provide a compelling rationale for clinical translation of ferroptosis-based therapies in this molecularly defined population.

The diagnosis should be based on a combination of morphological features and immunophenotype. It is recommended to use PAX8, CK7, HNF1-β, and Napsin A as a core immunohistochemical panel, while testing SOX17 can also help.

Ibrutinib is used clinically to treat specific B cell disorders; however, it is not currently approved to treat solid tumours. Data presented in OCCC cell lines complements clinical observations of a therapeutic response to ibrutinib in low-grade serous ovarian cancer. Ibrutinib demonstrates potential for the treatment of certain rare subtypes of ovarian cancer and should be further investigated.

NRAS was the most frequent mutation, followed by ARID1A, CDK4, CDKN2A, JAK2 and MYC, without a significant association with survival. These results emphasise the prognostic value of mitotic index and surgical completeness, while confirming the marked molecular heterogeneity of mucosal melanoma and the lack of a single dominant actionable alteration.

This case provides direct morphologic and molecular evidence of spatial clonal evolution in a multiple-classifier endometrial carcinoma. The clinical implications of this spatial heterogeneity remain uncertain and warrant further investigation.

Despite multiple adverse prognostic indicators, the patient has remained disease-free for over 5 years following adrenalectomy and adjuvant low-dose mitotane therapy. These findings suggest that GNAS activation may drive steroidogenesis while attenuating malignant progression, as demonstrated by integrated morphologic and genomic assessment in this case.

The results of this real-world study demonstrate that endometrial cancer is a complex disease, characterized by substantial molecular heterogeneity and varying biomarker distributions across histology, stages, and molecular subtypes. This real-world study supports the integration of comprehensive molecular profiling into routine practice to refine prognostic stratification and guide biomarker-driven therapies.

Pathway analysis revealed predominant WNT/β-catenin signaling in EBTs versus RAS-MEK-ERK pathway alterations in SMBTs resembling the seromucinous variant of ovarian endometrioid carcinoma, with additional involvement of PI3K-PTEN-AKT-mTOR and SWI/SNF chromatin remodeling pathways in both. These findings demonstrate that EBTs and SMBTs possess distinct morphologic and molecular profiles, expanding the molecular characterization of early ovarian endometrioid-type neoplasms.

This work provides an overview of current methodologies for neoantigen identification, advances in prediction and validation strategies, and the dynamic interplay between tumor-intrinsic and immune-related factors that regulate neoantigen expression. We also highlight recent clinical insights as well as novel analytical approaches and discuss challenges and future directions in this rapidly evolving field, emphasizing the potential of neoantigen-based therapies to transform cancer immunotherapy.

Due to the low mutation frequency of commonly studied genes, cumulative mutational burden may better explain the progression and pathogenesis of endometriosis-associated epithelial ovarian carcinoma than any single mutation. CTNNB1 may be associated with the development of endometrioid ovarian carcinoma. Future studies may consider the use of polygenic scores for risk assessment of endometriosis-associated ovarian cancer.

The integration of NGS and the subsequent use of matched targeted therapy significantly improved survival outcomes in selected patients with advanced BTC, highlighting the importance of precision medicine strategies.