TEST:

FusionPlex® Pan Solid Tumor v2 panel

This case represents the first reported instance of ESOS with an NTRK fusion. The rapid and sustained response to larotrectinib highlights the potential of precision medicine in managing rare and aggressive tumors, emphasizing the importance of molecular profiling to identify actionable targets.

Given that PDGFRA fusions with novel fusion partners may respond to tyrosine kinase inhibitor therapy, partner agnostic testing methods should be considered either up front or as reflex testing in patients with myeloid and/or lymphoid neoplasms with blood, bone marrow, or tissue eosinophilia.

The genetic alterations detected in these tumors demonstrated potential diagnostic, prognostic, and therapeutic value. We suggest that incorporating in-house ancillary molecular testing could greatly enhance the accuracy of salivary gland fine needle aspiration cytology and small biopsies, thereby better guiding surgical decisions and the use of targeted therapies.

Our AFPST assay with the Ion Torrent GeneXus sequencing is clinically validated as a highly accurate, sensitive, and specific assay for detecting gene fusions in solid tumors and sarcomas. It provides clinical utility in classification and therapy selection for patients with solid tumors and sarcomas. Our validation study and institutional experience suggest the Ion torrent GeneXus System is fully compatible with the Archer FUSIONPlex assay and analysis.

FUSIONPlex and VARIANTPlex libraries provide the same fusion and variant identification performance capability on all sequencing platforms tested, suggesting that both assays are sequencing platform agnostic.

We successfully assessed the performance of the QIAxcel Connect system for NGS library prep QC analysis. In addition, employing this system significantly diminished the utility of the library quantification from testing each individual library to testing 1 pooled library for each panel, and subsequently reduced reagent cost, labor cost, workflow complexity, and potential human errors.

Despite the growing knowledge of cancer biology and its translation to drug development, the overall impact of personalized treatments remains low. Access to comprehensive molecular tests covering properly all known actionable alterations and programs for a wide access to targeted therapies seem to be critical steps.

Based on histopathological and molecular results, the diagnosis of cryptococcal inflammatory pseudotumour was made. Only a few cases of cryptococcal inflammatory pseudotumours have been reported in the literature, mainly in HIV-positive patients. Our patient was not HIV-positive but ten months before the wedge resection, she had a type B2 thymoma treated with induction chemotherapy and consecutive resection (R1) as well as adjuvant chemotherapy.

"This report emphasis the importance of molecular testing in the differential diagnosis between PEComa and melanoma, especially when the tumor arises in a site typical of melanoma but showing an unusual morphology and immunophenotype. The detection of TFE3 fusion transcripts suggested the diagnosis of SNT PEComa, although it cannot be excluded that this and similar tumors represent a distinct diagnostic category."

When using 50ng SeraSeq® Myeloid DNA input (LGC Clinical Diagnostics, Inc.) and the VariantPlex Core Myeloid panel (37 gene targets), both the lyophilized VariantPlex and VariantPlex-HT detected 100% (22/22) known variants ranging from 3.8% to 20.4% allele frequency (AF). When using low-quality FFPE and the VariantPlex Complete Solid Tumor panel (430 gene targets), both workflows captured 28/28 (AF: 1.4%-20.2%) and 11/11 (AF:1.2%-18.9%) single nucleotide variants (SNVs) and Insertion and Deletions (InDels) when 50ng of SeraSeq compromised FFPE or 200ng Horizon Severe FFPE was used as input, respectively. The FusionPlex-HT workflow consistently showed increased library complexity using the FusionPlex Lung V2 panel with 20ng or 50ng of Seraseq RNA Fusion Mix v4 input.

A subset (10.3%) of multifocal PTCs had discordant molecular drivers and 90.0% of them were a combination of BRAF-positive and kinase gene fusion-associated PTCs, mostly with different histologic subtypes. Half of the cases had nodal metastasis and 40% (2/5) of them showed simultaneous involvement by tumors with discordant molecular drivers. These findings highlight the clinical importance of identifying such cases given the potentially different management with specific targeted therapies.

MET-exon-2 skipping was documented as a potential self-regulating mechanism of tumor cells by decreasing abundance of Met mRNA encoding a functional Met receptor. Our findings suggest that advanced stage non-small cell lung carcinomas may trigger one such regulatory event to balance cancerous growth of tumor against coexisting pathogenic mutations especially of genes from the MAPK pathways. These observations are novel and may help shed light on mechanisms that regulate tumor growth, facilitate biomarker development for prognostics, and help design therapeutic targets.