CTNNB1 mutation

With the largest IPN/ICPN cohort reported to date, our study provides a genome- and spatial transcriptome-level portrait of sequential carcinogenesis and differences in the anatomical location of biliary papillary neoplasms.

Several definite genetic mutations involved in GC were observed. Mutations were less frequent in post-eradication differentiated GC. However, because of small number of cases analyzed to identify carcinogenic differences, further analysis with a large number of cases and with strictly grading GC samples is needed.

P2, N=15, The First Affiliated Hospital of Sun Yat-sen University; The First Affiliated Hospital of Sun Yat-sen University

P1, N=70, Active, not recruiting, Eisai Co., Ltd. | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Jan 2025 --> Jan 2026

Moreover, the c.94G>T p. (Asp132Tyr) mutation in the CTNNB1 gene was detected. This study supports the combination of appropriate immunohistochemical and molecular markers, along with the presumptive histological diagnosis, and determines the correct classification of the lesion as APA and not as other malignant pathologies, allowing for the establishment of a treatment protocol adjusted to the biological reality of this pathology.

In conclusion, this study demonstrated that the S100-positive stroma of BCAs exhibits a neoplastic nature from a molecular perspective. While future studies are needed to confirm whether the S100-positive stroma originates from myoepithelial cells, BCAs morphologically display tricellular differentiation, with neoplastic spindle-shaped stromal cells along with a bilayered neoplastic epithelium.

Mutations in WT1, CTNNB1 and copy-neutral loss of heterozygosity of 11p15.5 provide possible genetic predisposition for the early initiation of bilateral WT. Our results provide comprehensive evidence and new insights regarding the separate initiation and early embryonic development of bilateral WT, which may benefit clinical practices in treating metastatic or refractory bilateral WT.

Lastly, CTNNB1 -mutated patients treated with atezolizumab plus bevacizumab combination had decreased presence of lymphoid aggregates, which were prognostic for response and survival. In conclusion, LNP-CTNNB1 is efficacious as monotherapy and in combination with ICI in CTNNB1 -mutated HCCs through impacting tumor cell intrinsic signaling and remodeling global immune surveillance, providing rationale for clinical investigations.

Lastly, in adult cancers, DICER1 alterations are associated with immune gene expression signatures and improved survival in response to immune checkpoint inhibitors. Together, our results identify clinical and biological properties regulating PD-L1 in Wilms tumor that may inform precision therapy approaches in pediatric immuno-oncology.

We conclude that LEF1 immunostaining is a useful surrogate marker for CTNNB1 mutations. It favourably complements β-catenin immunohistochemistry and outperforms the latter as a single marker.

This study confirms that spontaneous regression occurs in a significant proportion of patients and that two-thirds are treatment-free at 5 years. Initial tumor size, CTNNB1 mutation, and location should be factored into the initial decision-making process.

Post-operatively, adjuvant chemotherapy with mitotane was commenced because of histologically high-grade ACC...At both time-points, CTNNB1 mutations consistent with the primary tumor were observed in ctDNA, with the allelic ratio increasing over time from 8% to 27%. In conclusion, monitoring the ctDNA allelic ratio may be useful for evaluating disease progression in advanced ACC.