NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1)

Pan-TRK IHC has a false-positive rate of ∼4%, particularly in squamous cell carcinomas, underscoring the need for confirmatory NGS to validate IHC findings and assess fusion functionality. Functional NTRK1/2/3 fusions remain exceedingly rare in NSCLC, with a detection rate of 0.03% across our combined cohorts.

None of the cases had genomic variants in TERT or CDKN2A. We believe FGFR1 fusions constitute a distinct subtype of Spitz neoplasm and FGFR1 should be added to the list of Spitz-associated genomic fusions.

In addition, pathogenic germline variants in MITF, NTRK1, and BAP1 were identified in three patients; notably, the NTRK1 germline variant was accompanied by an independent somatic mutation in the same gene. Overall, these findings support liquid biopsy as a valuable approach for molecular profiling of CUP and highlight the critical importance of paired ccfDNA/gDNA analysis, including CHIP assessment, to accurately distinguish somatic, germline, and hematopoiesis-related variants.

Most "Invalid" results were attributable to RNA degradation and resolved with freshly cut sections. These findings support the Idylla GeneFusion Assay as a rapid and practical frontline tool for NTRK fusion detection, particularly in settings with limited tissue or need for expedited decision-making, with reflex next-generation sequencing recommended for "Equivocal" cases or when fusion partner identification is required.

In conclusion, Hi-C sequencing detects gene rearrangements crucial for diagnosis in an unbiased and molecular manner and showed high sensitivity and specificity in our study. These advantages of Hi-C sequencing offer help to improve the workflow of clinical pathology laboratories, diagnostic precision, and treatment of large B-cell lymphoma.

Collectively, these proteomic candidates illustrate the complex interplay of signaling, immune regulation, bone microenvironment, and metabolism in MDS. Their validation in clinical cohorts could enable early detection, refined risk stratification, and new therapeutic avenues, positioning proteomics as a central tool in the future management of MDS.

The patient was treated with temozolomide concurrently with radiotherapy, followed by tumor treating fields with adjuvant temozolomide...Various tyrosine kinase inhibitors, including entrectinib, larotrectinib, repotrectinib, and selitrectinib, along with bevacizumab, were considered to potentially prolong progression-free survival and overall survival and improve quality of life. We expect to highlight the rarity of this case while discussing the effectiveness of second-generation tyrosine kinase inhibitors in high-grade glioblastomas with rare gene fusions. We also hope to identify the appropriate timeline and treatment sequence for post-standard care, given the lack of official guidelines regarding cases this infrequent.

Malignant progression in meningiomas appears to reflect a process of clonal evolution shaped by genomic instability and therapeutic selection pressures. In this context, the observed association between irradiation and adverse outcomes underscores the need to critically reassess its role, while surgical resection remains the cornerstone of management.

P1/2, N=67, Recruiting, D3 Bio (Wuxi) Co., Ltd | Active, not recruiting --> Recruiting | Trial completion date: Apr 2028 --> Aug 2028 | Trial primary completion date: Apr 2028 --> Aug 2028

Knockdown of NTRK1, which encodes TrkA, reduced cell viability and sensitized ATC cells to paclitaxel. Entrectinib was well tolerated at the administered dose, with no significant changes in body weight and serum biochemical markers. Collectively, these findings identify TrkA as a potential therapeutic target in ATC and support further investigation of entrectinib-based combination strategies to improve ATC treatment outcomes.

Continuous genomic monitoring is essential for identifying resistance mechanisms and guiding precision therapy. Future studies should explore the impact of different fusion partners on tumor behavior and therapeutic response.

RAF/BRAF-driven mesenchymal tumours possess a broader clinicopathologic spectrum than traditionally recognised, frequently affecting adults and deep/visceral sites. Their inherently variable immunophenotypes and the presence of high-grade morphologic features do not strictly predict an aggressive clinical trajectory. Comprehensive molecular profiling is essential to refine diagnostic criteria, accurately identify these neoplasms, and elucidate the genomic events associated with tumour progression.