KIT fusion

Two patients died from infection following transplantation. Afatinib plus allo-HSCT may be an effective and safe new treatment strategy for RUNX1-RUNX1T1 positive AML patients with KIT-D816 mutation.

2 patients did not achieve continuous RUNX1: : RUNX1T1 negative after preemptive therapy with Decitabine (DAC) and donor lymph infusion (DLI), and then was treated with Avapritinib, one's RUNX1: : RUNX1T1 fusion achieved continuously negative after 1 month treatment of Avapritinib, the other's achieved continuous negative after 7 months treatment of Avapritinib. Avapritinib is safe and effective in the prophylactic and preemptive treatment of AML with KIT mutation after allo-HSCT in children, which provides a clinical drug for the prevention of relapse after transplantation.

We suggest an oncogenic mechanism that involves the overexpression of KITLG caused by its rearrangement with HMGA2, leading to the constitutive activation of KIT kinase. While MDM2 amplification was observed in both the primary tumor and the relapsed tumor, the HMGA2::KITLG was only present in the relapsed tumor, indicating the role of HMGA2::KITLG in disease progression.

Secondary rearrangement involving EML4-ALK which places the fusion gene under control of a new promoter may be a novel mechanism of resistance to crizotinib in IMT (and potentially other ALK-fusion-driven malignancies). Alectinib, a more potent ALK inhibitor, overcame resistance in this case. More broadly, this study exemplifies the importance of molecular testing in the setting of resistance to targeted therapy to inform clinical decision making.

This type of mutation is mostly found in the non-tyrosine kinase domain. Investigating the PDGFRA map and PDGFRA inhibitors has significant exploratory value.

Our results demonstrated the synergistic effect of Chidamide with Cladribine on cell growth arrest, cell cycle arrest, and apoptosis in AML and primary cells with genetic defects by targeting HDAC2/c-Myc/RCC1 signaling in AML. Our data provide experimental evidence for the undergoing clinical trial (Clinical Trial ID: NCT05330364) of Chidamide plus Cladribine as a new potential regimen in AML.

Our analysis confirms that most cases of EMC are positive for INSM1. However, the diagnostic utility of this marker is limited by the fact that only 50% of cases show a strong INSM1 expression in most tumour cells. Furthermore, our study highlights that EMC with alternative gene partners may present with unusual morphology.

Moreover, laboratory workflows are distinct for FFPE tissue specimens and liquid biopsies as well as time-consuming for sample quality control assays. In summary, the DNA-based next-generation sequencing approaches may be suitable for routine molecular pathology diagnostics on careful data interpretation and further optimization of the technical and laboratory workflows.

Molecular detection is an indispensable technique for diagnosing cellular EMCs. The KIT mutations noted in this case report may offer fresh insights into EMCs treatment options.

"The introduction of NGS techniques provides additional information about tumour molecular alterations that can aid the multimodal management of glioma patients. Patients with gliomas positive for particular targetable gene fusions may benefit from experimental therapeutics, enhancing their quality of life and prolonging survival rates."

Besides identifying several rare or novel kinase fusions genes, our analysis also revealed various additional mutations including recurrent PIK3CA point mutations. Although their significance is unknown, they might be responsible for progression of tumors with LG morphology (LNT, FTPH) into tumors with HG morphology and/or acquisition of a more aggressive biological potential. Targeted therapy is effective and significantly aids in successful treatment.

Cas9/gRNAs were transduced into Jurkat cells ± HMGN1 overexpression, activated with doxycycline and stained with TSLPR (CRLF2/IL-7Rα dimer) for single cell sort and clonal expansion...Using CRISPR/Cas9 in an in vitro model, we demonstrate that enforced high expression of HMGN1 alters DSB repair mechanism, favoring PAR1 deletion and the subsequent formation of the P2RY8-CRLF2 gene fusion, with attendant higher expression of STAT5 target genes. Understanding the role of HMGN1 in the disproportionate number of DS-ALL patients who are diagnosed with CRLF2r has the potential to lead to novel therapeutic interventions, in this high-risk group of patients where efficacious therapeutic options are currently poor.

The obtained frequencies, and genetic and patients' characteristics are in concordance with the literature data, ensuring a reliable detection of this challenging ALL subtype. The proposed algorithm allows detection of Ph-like ALL at reasonable cost and acceptable workload.

ALK fusion prevalence is very similar for Chile (3.67%, N=2142), Brazil (4.05%, N=1013) and Peru (4.59%, N=675). Whereas a comparison between OFA and SofC assays showed similar sensitivity, OFA had significantly higher specificity and higher positive predictive value, which opens new opportunities for a more specific determination of ALK gene rearrangements.

Furthermore, mRNA expression levels may be used for predicting cases harboring TFEB amplification, thereby streamlining testing. This assay enables accurate molecular detection of multiple subtypes of MiT-RCCs in a convenient workflow.

Herein novel putative pathogenic gene fusion UNC5D-NRG1 is described. The potential role of immunohistochemistry in tumor identification should be further addressed.

Given the rarity of Skene's gland adenocarcinoma, it is uncertain whether the same grading and prognostic criteria that are currently used for prostatic cancer apply here as well. It is also unclear what treatment strategy should be applied, but according to the available literature, it seems that local excision or wide surgical resection could represent sufficient therapeutic modalities.

Legal entity responsible for the study: The authors. Funding: Supported by Charles University Research Fund (Progres Q39) and MH CZ-DRO (University Hospital Plzen-FNPl, 00669806).

The overall frequency of tumors with NRG1 fusion in our study (0.18%) is comparable to that being reported in the literature. We also confirm that lung adenocarcinoma is the most frequent tumor presenting NRG1 fusion. The spectrum of tumors cannot be fully compared due to a low number of cases identified.