BRAF fusion

These findings may represent a previously undescribed type of salivary gland tumor. However, additional reports of similar lesions are necessary for definitive characterization.

P2, N=26, Active, not recruiting, University Health Network, Toronto | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

Integrated pathologic-molecular analysis is essential for accurately classifying supratentorial papillary glioneuronal tumors. Classic PGNTs are molecularly defined by recurrent PRKCA fusions, while BRAF-altered cases warrant reclassification.

Osimertinib plus selumetinib demonstrated minimal response in patients with EGFR-mutated advanced NSCLC with BRAF alterations following disease progression on first-line osimertinib. The safety profile of the combination was consistent with the known profiles of the two individual drugs; no new safety signals were identified. Overall, the risk-benefit profile suggests further evaluation of this combination is not warranted.

BRAF fusions are exceedingly rare in salivary gland tumors and may occur across different histologic types. Given their potential sensitivity to MEK or next-generation RAF inhibitors, comprehensive molecular testing is essential for identifying patients who may benefit from targeted therapies.

Pulmonary toxicity was observed in patients receiving lorlatinib combined with anti-GD2 immunotherapy or chemotherapy. These preliminary findings suggest potential efficacy of frontline lorlatinib in ALK-driven neuroblastoma, highlight molecular determinants of sensitivity, and reveal challenges of resistance and treatment-related toxicity.

DNA methylation profiling revealed that the second and third specimens were classified as diffuse midline glioma, H3 K27-altered. This case suggests that the H3-K27M mutation, MAPK pathway activation, and loss of p16 expression contribute to tumorigenesis, while clonal proliferation of the tumor harboring the NF1 mutation may play a role in malignant progression.

These findings expand the molecular spectrum of thyroblastoma beyond the canonical DICER1-driven paradigm and suggest that DICER1-wildtype cases may represent a distinct biological subgroup. The identification of alterations affecting TERT and MAPK pathways highlights potential therapeutic vulnerabilities and supports the clinical value of comprehensive genomic profiling in ultra-rare thyroid malignancies.

P1, N=6, Recruiting, Ipsen | Not yet recruiting --> Recruiting

These findings suggest additional molecular alterations associated with tumor progression within the piloid lineage. To our knowledge, this is the first report providing comprehensive, paired molecular characterization of both PA and HGAP in the same patient, offering insight into their potential evolutionary relationship.

This finding expands the molecular spectrum of uterine mesenchymal neoplasms and defines a novel kinase-driven subset. The BRAF fusion indicates MAPK pathway activation and raises the possibility of a distinct entity or a novel pathogenetic pathway in HG-ESS, with potential therapeutic implications.

P2, N=35, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Mar 2027