BRAF fusion

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

Serial cell lines from a patient with EGFR L858R and MET amplification (PE5345), after resistance to osimertinib and capmatinib through gradual escalation of drug exposure in vitro (PE5345 os/cp R) and after clinical resistance to osimertinib and capmatinib (PE5867), were propagated...Osimertinib plus trametinib reversed resistance. PE5345 os/cp R overexpressed EGFR, which was inhibited by afatinib...Amivantamab induced significant ADCC against both MET-amplified EGFR TKI-resistant cancer and resistant cells after dual EGFR/MET inhibition. Understanding resistance mechanisms may provide clues for subsequent therapy.

Molecular analysis demonstrated BAP1 mutation and a novel fusion involving PDZRN3::BRAF. Our finding expands our current understanding of the molecular landscape and pathogenesis of BIMT.

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