Background: Kinase-rearranged spindle cell sarcomas are characterized by unique molecular features. The advent of next-generation sequencing (NGS) has enabled the detection of a multitude of kinase fusions, thereby contributing to the accurate categorization of these tumors.
Case Presentation: A 37-year-old woman experienced the fourth recurrence of a cranial base tumor 25 years following the initial surgery and radiation therapy. Histological analysis disclosed spindle-shaped and oval tumor cells, along with a high number of mitotic figures. Immunohistochemistry showed a null immunophenotype, negative for pan-TRK, S-100, CD34, pan-CK, GFAP, and Olig2. Molecular analysis of the tumor tissue identified a novel ACVR2A::RAF1 fusion, comprising the first four exons of ACVR2A and the last nine exons of RAF1. The resulting fusion protein retains the extracellular and transmembrane domains of ACVR2A, while its kinase domain is replaced by the kinase domain of RAF1. This hybrid protein likely contributes to tumorigenesis by activating RAF1 signaling in response to ACVR2A ligands from the TGF-β superfamily.
Treatment And Outcome: The patient was treated with the MEK1 inhibitor Trametinib, 2 mg per time and once a day. One month later, MRI showed significant tumor shrinkage and pain relief.
Conclusion: The ACVR2A::RAF1 fusion represents a novel genomic profile in RAF1-rearranged spindle cell sarcoma, offering a rational basis for targeted therapy. This case highlights the importance of molecular diagnostics in identifying actionable targets and guiding treatment, potentially leading to significant clinical benefits.
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http://dx.doi.org/10.1002/gcc.70033 | DOI Listing |
Genome Res
March 2025
Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA;
Gene fusions are found as cancer drivers in diverse adult and pediatric cancers. Accurate detection of fusion transcripts is essential in cancer clinical diagnostics and prognostics and for guiding therapeutic development. Most currently available methods for fusion transcript detection are compatible with Illumina RNA-seq involving highly accurate short-read sequences.
View Article and Find Full Text PDFWorld Neurosurg
March 2025
Neurosurgery Unit, Department of Neuroscience "Rita Levi Montalcini", "Città della Salute e della Scienza" University Hospital, University of Turin, Turin, Italy.
Objectives: The robot-assisted cortical bone trajectory (CBT) screw placement is safer than the traditional fluoroscopy-assisted approach. This is the first technical note reporting a novel technique of robot-assisted CBT screws placement with a subfascial transmuscular approach.
Technical Note: After a lumbar interbody cage position, the second step consists in the robot-assisted placement of CBT screws in a prone position.
Biochim Biophys Acta Proteins Proteom
March 2025
Department of Biotechnology, National Institute of Technology Durgapur, Durgapur, 713209, India. Electronic address:
The conserved invasion plasmid antigen D (IpaD) protein demonstrates broad protective capabilities against bacillary dysentery caused by Enteroinvasive Escherichia coli (EIEC) and Shigella. However, the instability of the IpaD protein at room temperature limits its therapeutic potential. The stabilization and efficient production of functional recombinant proteins remain critical challenges in therapeutic and vaccine development.
View Article and Find Full Text PDFClin Neurol Neurosurg
March 2025
Vail-Summit Orthopaedics and Neurosurgery, 180 S Frontage Rd W, Suite 2700, Vail, CO 81657, United States.
Objectives: To implement an integrated anesthesia and surgery protocol of improved postoperative pain control to facilitate transitioning of minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) from a hospital to an ambulatory surgery center setting by lowering postoperative (in-facility) narcotic consumption and length of stay (LOS) transitioning from general to awake spinal anesthesia.
Methods: A retrospective cohort study of 180 patients who received awake or general anesthesia (GA) MI-TLIF from 2017 to 2023.
Results: Among 180 MI-TLIF patients, 101 (56 %) received awake protocol and 79 (44 %) received general anesthesia.
Pathol Res Pract
March 2025
Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea; Cardiovascular Research Institute, Kyungpook National University, Daegu 41944, Republic of Korea; BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea. Electronic address:
Next-generation sequencing (NGS) technologies have revolutionized bone cancer research, enabling detailed insights into the genetic, transcriptional, and epigenetic layers of these malignancies. This overview discusses the pivotal role of NGS in enhancing the diagnosis, prognosis, and treatment of primary bone cancers such as osteosarcoma, chondrosarcoma, and Ewing sarcoma. By facilitating the identification of novel genetic mutations, gene fusions, and epigenetic alterations, NGS supports the development of personalized medicine approaches and targeted therapies, significantly impacting clinical outcomes.
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