BRAF fusion

Although surgical resection may be associated with improved survival, interpretation is limited by selection bias. No single molecular alteration reliably predicts prognosis, highlighting the need for prospective multicenter studies with standardized molecular profiling.

The findings in this patient underscore the importance of extending molecular genetic studies to patients with squamous histology who lack toxic habits or known risk factors. Gene alterations such as BRAF rearrangements may not only predict the response to immunotherapy-based treatments but also represent a promising avenue for the development of new therapeutic strategies.

This study shows that DMDTCs are characterized by dysregulated phosphorylation signalling, accompanied by chromosomal instability and aberrant methylation, thus underscoring DDR gene-targeted therapy as a promising strategy.

P1/2, N=31, Not yet recruiting, Universitaetsklinikum Heidelberg AR

P1/2, N=217, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jul 2026 --> Mar 2027 | Trial primary completion date: Jul 2026 --> Jan 2026

P1/2, N=28, Not yet recruiting, Universitaetsklinikum Heidelberg AR

Infants, less than 1 year, with chiasmatic gliomas (ICG) present a major therapeutic challenge due to large tumor size, decreased vision, rapid progression, and poor response to vincristine/carboplatin chemotherapy. We report two infants with BRAF-fused ICG presenting at age 5 months with nystagmus and diencephalic syndrome. Significant tumor progression occurred after only 6 weeks on chemotherapy and showed dramatic response to the addition of trametinib.

Focal copy-number variations on Chr7q suggestive of BRAF fusions were observed in 5/6 fusion-positive pilocytic astrocytomas. These findings demonstrate that off-target reads from minimal targeted NGS panels can generate genome-wide CNV profiles, comparable to methylation array data, without the need for additional assays or specialised probe designs.

We describe a case report of nasal nonkeratinizing squamous cell carcinoma- HPV-high risk (HPV-HR) positive and harboring an MKRN1::BRAF fusion. We further discuss the significance of these findings, integrated in the context of current literature.

MRI-based machine learning models may support noninvasive prediction of BRAF mutation status in pLGG. FLAIR is the best-predicting single sequence, but multisequence integration was associated with improved and more balanced performance. These findings support multisequence radiomics as a promising tool to guide precision treatment in pLGG, particularly when tissue sampling is not feasible.

HGAP represents a clinically aggressive and molecularly distinct high-grade glioma, clearly separable from pediatric and adult PA. Its poor prognosis and unique genetic drivers justify its recognition as a new entity. Accurate molecular profiling is essential for diagnosis and management of these tumors, and the poor survival outcomes observed in HGAP highlight the need for further larger cohort studies to identify optimal therapeutic strategies.

As expected, none of the BRAF KIAA1549 fusion+ pLGG tumors were sensitive to dabrafenib treatment. Two out of the three tumors demonstrated predicted sensitivity to trametinib, whereas one tumor did not. While no clinical correlates were measured in this proof-of-concept study, this mixed response to MEK inhibition on SLiCE is representative of heterogeneous real-world clinical responses. Together, these data demonstrate the feasibility of SLiCE to become a new functional biomarker of response in a tumor type where functional models are exceptionally rare, establishing a foundation for future individualized treatment strategies.