TEST:

Archer® FusionPlex® Oncology Research Kit

Targeted therapy was actually started for 95 pts (16%), with 15 (16%) pts treated with ivosidenib for IDH1 mutations, 63 (66%) with FGFR2 inhibitors for FGFR2 alterations, 3 (3%) with immune checkpoint inhibitors (ICIs) for MSI-H, 9 (10%) with BRAF+MEK inhibitors for BRAFV600E mutations and 4 (4%) with HER2 inhibitors for HER2 amplification... NGS is feasible in daily clinical practice and it should be performed, as recommended, for all pts affected by advanced BTC, since biomarker-directed treatment for BTCs has clinically meaningful benefit in pretreated patients.

"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."

Additional molecular analysis is ongoing. Close follow-up is recommended.

Namely, an aggressive spindled and epithelioid rhabdomyosarcoma often of craniofacial bones with a propensity to diffusely express keratins. Awareness of this entity will help prevent misdiagnosis as sarcomatoid carcinoma and possibly allow for personalized therapy given their frequent ALK overexpression.

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.

The clinical benefit with KIT inhibitors, such as imatinib, remains to be determined. The recognition of BRAF fusion-positive GISTs is critical as it may be associated with a low level of KIT expression and may result in diagnostic challenges with significant impact on therapeutic management. The clinical benefit with KIT inhibitors, such as imatinib, remains to be determined.

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.

NKX2-2 and NKX3-1 staining were negative in all cases. Thus, even though the overlap between the 2 entities is limited to the presence of few thick-walled cysts lacking endothelial lining in the benign vascular malformations, the spectrum of benign tumors containing NFATC2 fusions should be expanded and contains not only SBC in the young, but also vascular malformation/hemangioma in elderly patients.

NTRK1-3 fusions using an RNA-based sequencing approached could not be detected. This stresses the importance of confirmation of immunohistochemistry results by molecular methods.

Presence of XPO1 pathogenic mutations was associated with a poor survival in both the entire NSCLC cohort and the adenocarcinoma subgroup . Further studies of this negative association at the molecular level along with effect of other co-existing mutations can result in development of novel treatment strategies.

These results suggest the possibility of a previously undescribed soft tissue neoplasm characterized by a uniform spindle cell phenotype arranged in a storiform and fascicular pattern, expressing S100 protein and harboring NACC1-related fusions. The biologic behavior of this tumor remains to be determined.

We developed a novel and efficient breakpoint targeted fusion detection RNA-seq assay from extracted TNA from FFPE samples that can comprehensively profile thousands of clinically actionable RNA fusions and aberrant RNAs in solid tumors.

"In summary, especially RNA-based parallel sequencing approaches are potent tools for reliable detection of targetable gene fusions in clinical diagnostics."

Specific WEFCs were detected according to the panel selected.

Our results demonstrated the importance of thorough molecular examination of all newly diagnosed brain tumors. Similar to mutations, gene fusions can serve as oncogenic drivers in brain tumors as well as therapeutic targets. Patients with tumors that harbor specific gene fusions may be treated with emerging targeted therapies.

Taken together, our findings indicate that PAs and MECs arising in the breast resemble their salivary gland counterparts not only phenotypically but also at the genetic level. Furthermore, our data suggest that the molecular analysis of breast PAs and MECs might constitute a useful tool to aid in their differential diagnosis.

In the remaining 2 cases, ALK gene rearrangements were demonstrated by fluorescence in situ hybridization. Unlike adult mesotheliomas, which are tightly linked to asbestos exposure, often show loss of BAP1 expression and have complex karyotypes, ALK-rearranged mesothelioma appears to be similar to other fusion-positive mesotheliomas, such as those harboring EWSR1/FUS-ATF1 fusions, sharing significant morphologic overlap, occurring in young patients and displaying a simple, translocation-driven genetic profile.

Eventually, no driver alteration was found in 2/162 GISTs (1.2%) and three samples (1.9%) failed analysis. Our study shows that a comprehensive targeted NGS approach is feasible for routine mutational analysis of GIST, thereby substantially reducing the number of Wild Type GISTs, and highlights the need to optimize assays for challenging KIT exon 11 alterations.

"This FusionPlex assay offers a single method for COO classification, mutation detection, and identification of important translocations in DLBCL. Although not replacing traditional testing, it could offer useful data when limited tissue is available."

"Moreover, a previous consensus on the analysis and reporting following international guidelines would be preferable to improve the concordance in results among centers. Our study shows the challenges posed by NGS methodology and the need to consider several aspects of the chosen NGS-targeted approach and reach a consensus before implementing it in daily practice."

Conclusion The newly detected LTBP1-ALK fusion in the described ESN carries a potential target for biological treatment. As genetic analysis becomes more accessible, additional novel alterations are expected to be found in ESN and may serve as targets for biological treatment.

Novel and rare fusions partner can be identified by targeting one gene fusion partner only. Mutations/Deletions leading to exon skipping events can be verified.

Conclusion The newly detected LTBP1-ALK fusion in the described ESN carries a potential target for biological treatment. As genetic analysis becomes more accessible, additional novel alterations are expected to be found in ESN and may serve as targets for biological treatment.

Conclusion The tumor was diagnosed as a spindle cell tumor with ETV6-NTRK3 fusion with differential diagnoses infantile fibrosarcoma and ALK negative inflammatory myofibroblastic tumor (IMT). The morphology, the interspersed inflammatory cells and the localization are more in line with IMT.

Conclusion The newly detected LTBP1-ALK fusion in the described ESN carries a potential target for biological treatment. As genetic analysis becomes more accessible, additional novel alterations are expected to be found in ESN and may serve as targets for biological treatment.

This CTA is currently used to pre-screen & select patients for the phase IB trial with the porcupine inhibitor ETC-1922159 (NCT02521844) ongoing in Singapore and USA...Funding: BMRC, NRF and NMRC Singapore. Clinical trial identification: NCT02521844.