TEST:

FusionPlex® Pan Solid Tumor v2 panel

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.

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.

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.

The resulting fusion protein comprises the oligomerization domain of NUMA1, which is predicted to cause constant activation of the tyrosine kinase domain of NTRK1. The recognition and accurate diagnosis of these tumours are important due to the availability of potential targeted therapeutic options.

NBL1 is a novel partner gene of USP6 translocation, which is a biomarker for diagnosis of aneurysmal bone cyst or fibroblastic/myofibroblastic tumors. It is interesting to note that common translocations usually result in fusion proteins and are associated with malignant tumors. On the contrary, USP6 translocations usually do not result in fusion proteins and are seen in benign tumors.

Overall, we found that a large NGS-based cancer panel was successful in detecting diagnostic and actionable gene translocations and variants associated with salivary gland neoplasms using stored FFPE tissue. Approximately half of the cases that were successfully sequenced in this study demonstrated a cancer-associated gene alteration with potential diagnostic and therapeutic value for these patients. Ancillary molecular testing has the potential to significantly improve the accuracy of salivary gland FNAC and small biopsies.

MET exon 2 is a large exon with 1214 bp and its skipping results in a Met mRNA that fails protein translation. It was hence regarded as a regulating mechanism to decrease its functional mRNA abundance. Our findings on its association with advanced stage lung adenocarcinomas and coexisting pathogenic mutations of other genes, especially genes from the MAPK pathways, are novel.

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.

Targeted therapies with multi target tyrosine kinase inhibitors may be considered for selected cases.Conclusion ASPS of the cervix is a rare entity with propensity to metastasize. Early diagnosis and surgical resection with clear margins are important for a more favourable prognosis.

These findings indicate that approximately 1.5% of Brazilian NSCLC patients harbor NTRK fusions and may benefit from targeted therapies. Using multiple methods can improve detection rates.; Cell and molecular biology; Endoscopy and interventional pulmonology; Epidemiology; Respiratory intensive care

Driver gene fusions were identified in 8.5% of PTCs and were clinically relevant given the emerging targeted kinase inhibitor therapy. Of the 1.6% of cases for which no driver alteration was detected, the specificity of drivers tested and tumor classification require further investigation.

As hypothesized, we identified fusions that the NCI-MATCH screening had missed, detailing sequencing technology improvement that could be broadly applicable to many clinical laboratories sequencing tumors. Clinical trial information: NCT02465060.

In this study, comparison of translocation detection using DNA and RNA-based NGS approaches revealed a high concordance between the two assays and were equally valuable for identifying actionable targets. These findings provide confirmatory support for the complimentary use of DNA- and RNA-based NGS approaches to most accurately identify clinically relevant translocations thereby providing more comprehensive results to help guide cancer treatment strategies.

In this post-2017 WHO classification cohort of 554 consecutive PTCs, BRAF V600E mutation is highly prevalent in 87% of the cases. RAS mutations account for only 1.1% of the cases and half of them are classified as encapsulated follicular variant of PTC. Kinase gene fusions are identified in 8.5% of the cases and are clinically relevant given the emerging targeted kinase inhibitor therapy.

"Integrated DNA Technologies, Inc....announced it closed on the purchase of Next Generation Sequencing (NGS) research assays from Invitae Corporation (NYSE: NVTA) under the trademarked name Archer. The integration of IDT’s portfolio with the acquired NGS research assays—which have been foundational in researching novel cancer fusions—will empower labs with an all-in-one solution to uncover biomarkers and advance cancer discoveries. The transaction enables IDT to expand its existing operations, build upon the legacy Archer portfolio, and welcome more than 100 new associates globally....Transaction Details-IDT purchased Archer NGS research assays—which reported high double-digit growth since 2019—from Invitae for cash consideration of approximately $48 million, subject to certain adjustments. The transaction is structured as an asset deal and includes a license to intellectual property related to the AMP technology."

Albeit ARR and SFU showed lower sensitivity, the use of additional fusion-detection tools can contribute to reinforcing or extending the output obtained by ADx, particularly in the case of low-quality input data. Overall, our results sustain the clinical use of NGS for the detection of fusion transcripts in FFPE material.

We successfully validated the OncoPanel NGS assay to simultaneously detect fusions, oncogenic splicing events, and expressed hotspot SNVs with as little as 20 ng of nucleic acid. This is advantageous for cases with limited input, such as lung core needle biopsies.

A commercially available NGS gene fusion assay allowed accurate and reproducible identification of fusions involving 137 target genes. Extraction of total nucleic acid (both DNA and RNA) preserves limited tumor material and allows future genomic testing. The adaption of a commercially available AMP-based NGS gene fusion assay allowed rapid implementation, reduced development cost, and decreased maintenance burden to enhance patient care.

BCCP is an aggressive type of prostate cancer challeng-ing to diagnose based on routine protocols. This results in delayed diagnosis & treatment and thus poorer prognosis. Patients with this subtype of prostate cancer need appropriately designed, and maybe a totally diferent follow-up regimen independent of PSA, as it's of no use in BCCP patients.

"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."

"In our cohort, ALK-rearrangements were predominantly observed in adenocarcinoma in non-smokers in younger age group. Patients with concurrent TP53 mutations had worse PFS with 57% patients manifesting resistance to first line TKIs. Testing for TP53 in patients with ALK-rearranged NSCLC and repeating mutational analysis in case of disease progression on ALK-TKIs may be beneficial in planning treatment options and improving survival."

The GENEFUSION assay is an accurate method for rapid fusion detection in ALK, ROS1, RET, and MET exon 14 splice variants. Due to the limited number of NTRK fusion positive cases analyzed, the performance of this gene is unclear. Further evaluation of non-targeted fusions is necessary to evaluate the performance of expression imbalance.

"Our preliminary experience indicates that a focused NGS approach using low-throughput compatible assays is sufficient to guide molecular therapy in the majority of patients. More advanced plan ning of individualized targeted treatments and straightforward access to approved compounds for off-label use may be more effective than broader NGS analyzes to increase clinical benefits from precision oncology."