BRAF fusion

Demonstrating the mutation carried by the tumor is very critical in this regard. The purpose of this article is to focus on the treatment of thalamic glioma in pediatric patients in light of molecular information.

Gene panel testing identified TMEM178B-BRAF fusion and subclonal PIK3CA mutations in the liver metastasis, in addition to ARID1A and CTNNB1 mutations that were shared with the endometrial tumour. This is the first report of an endometrioid carcinoma transforming into a high-grade neuroendocrine tumour associated with TMEM178B-BRAF fusion.

The most common molecular signature of these tumors is BRAF alterations, including rearrangements. The primary differential diagnosis is infant-type hemispheric glioma and given the similarities, pathologists must remain careful to ensure accurate diagnosis.

P1/2, N=50, Recruiting, St. Justine's Hospital | Not yet recruiting --> Recruiting

An inactivating ASXL1 variant and an in-frame KDM5B::LPGAT1 fusion were identified in one melanoma; paternal disomy of 11p15.5 in both embryonal rhabdomyosarcomas. Mesenchymal tumors and melanomas showed distinct transcriptional profiles enriched in muscle and synapse organization and epidermal differentiation genes, respectively.

NGS identified an AKAP9 (exon 32)::BRAF (exon 9) fusion, without TERT promoter mutations or other high-risk alterations. This case highlights a rare molecular subset of Spitz melanocytoma and underscores the importance of integrated molecular and histopathological assessment for accurate diagnosis, prognostic evaluation, and potential targeted therapy.

Trametinib is useful in NRAS-driven leptomeningeal melanoma in children, but not sufficient to prevent relapse, and can be helpful in NRAS-driven leptomeningeal dysplasia. It is very helpful symptomatically in BRAF fusion-driven cutaneous disease, where a reduced dose after initial response appears to sustain efficacy and reduce adverse effects.

High [18F] Fluciclovine uptake in pilocytic astrocytoma may reflect amino acid transporter expression, which may lead to overestimation of the WHO grade. Awareness of this pitfall is essential in pediatric neuro-oncology.

Dabrafenib plus trametinib has shown superiority over chemotherapy in pediatric low-grade gliomas and activity against high-grade diseases. Larotrectinib and entrectinib provide tumor-agnostic options for NTRK-fusion-positive tumors with central nervous system penetration. Selumetinib offers clinical benefits in NF1-associated plexiform neurofibromas and shows promise for treating NF1-related low-grade gliomas. Tovorafenib, a type II RAF inhibitor active in BRAF-altered tumors (including BRAFKIAA1549 fusion), achieved robust responses, thereby leading to FDA approval. ONC201 (dordaviprone) has received accelerated approval for the treatment of H3 K27M-mutant diffuse midline gliomas, with Japanese trials and patient-initiated programs expanding access. Abemaciclib, a CDK4/6 inhibitor, is under phase II evaluation for pediatric high-grade glioma and diffuse midline glioma, including sites in Japan. Neurosurgeons play a pivotal role in securing high-quality biopsies, thus enabling comprehensive molecular diagnostics and facilitating enrollment in international trials. This review summarizes current targeted therapies and ongoing studies and outlines practical considerations for integrating precision oncology into pediatric neuro-oncology in Japan.

The patient with EML4::ALK fusion was treated with alectinib with partial response...These finding further suggest that SMARCA4d-UT and carcinomas with SMARCA4 loss may be on the same spectrum of disease, and accurate histologic distinction between these lesions may be challenging. A unified terminology may be beneficial for appropriate diagnosis and treatment.

Assessment with green chemistry tools yielded favourable eco-scores (ComplexMoGAPI 90, AGREE 0.61, BAGI 70, RAPI 92.5, EVG Q2, and RGBfast 97.5%). This validated RP-UPLC procedure offers reliable, sensitive, and sustainable Tovorafenib analysis, supporting both efficient pharmaceutical quality control and environmental sustainability.

MM arising within CGMN poses diagnostic and therapeutic challenges. While molecular and epigenomic profiling supports accurate classification and understanding of disease biology, the role of immunotherapy remains uncertain-marked by reduced efficacy and significant immune-related toxicity. A multidisciplinary approach is essential to guide management and improve outcomes in this rare pediatric malignancy.