KIT mutation

Sunitinib for c-KIT mutations did not meet the primary end point, but in this small sample size, a potential signal cannot be ruled out. Rate of eligible c-KIT mutations was low, affecting accrual to this arm.

We describe the clinical course and the outcome with the use of avapritinib, midostaurin, and decitabine-cedazuridine. Trial Registration: ClinicalTrials.gov identifier: NCT00782067.

Our findings suggest that both C-MYC and EGFR may be overexpressed and/or amplified in GISTs, indicating their potential prognostic role. This could also pave the way for therapeutic strategies targeting these proteins.

The standard treatment includes surgery and imatinib for metastatic cases; however, resistance to tyrosine kinase inhibitors remains a significant hurdle, especially in pediatric and wildtype GISTs. This highlights the need for advanced therapeutic strategies and emphasizes the importance of molecular profiling in guiding treatment decisions and improving outcomes for GIST patients.

The results showed that QLNC-3A6 showed fast absorption rate, rapid distribution and slow metabolic elimination in canine plasma. The results of the main PK parameters including λz, T1/2λz, Cmax, Tmax and AUClast were 0.07 ± 0.01/h, 11.00 ± 2.57 h, 50.88 ± 31.94 ng/mL, 9.08 ± 11.57 h and 836.48 ± 230.53 ng h/mL, respectively.

The study showed that brisk tumor-infiltrating lymphocytes and stromal tumor-infiltrating lymphocytes were a marker for disease progression, and for response to immunotherapy strategies. To validate these findings on a larger scale, further research is warranted through a multicenter study with a larger cohort and additional genetic and translational analysis.

P=N/A, N=6, Completed, Daiichi Sankyo Co., Ltd. | Active, not recruiting --> Completed | Trial completion date: Mar 2025 --> Oct 2024

More data are needed to further understand the role of adjuvant radiotherapy. Molecular markers, such as KIT and BRAF mutations, should be examined.

Our study provides an example of implementation of molecular profiling in an academic pre-screening program. Further analysis will investigate treatment matching rates, drug access schemes, and their impact on treatment efficacy and survival.

In this updated exploratory analysis from INTRIGUE, OS was longer for ripretinib vs sunitinib for pts with KIT exon 11 + 17/18 mutations identified by baseline ctDNA. The safety profile was consistent and more favorable for ripretinib vs sunitinib in these pts. Previously presented at the 2024 ESMO Sarcoma and Rare Cancers Congress.

These results clearly demonstrate that detection of clinically relevant mutations in mRNA extracted from routinely processed decalcified archival bone marrow trephines is not only possible in a reliable fashion but under many circumstances advantageous. This enables the direct correlation of genomic data with high-quality morphological evaluation.

ctDNA-based analysis facilitates assessment of disease status and genomic profiles, thus potentially assisting in identifying optimal therapeutic strategies for advanced GIST patients.

P1/2, N=94, Recruiting, Deciphera Pharmaceuticals, LLC | Trial completion date: Jun 2027 --> Mar 2029

P=N/A, N=61, Completed, CStone Pharmaceuticals | Active, not recruiting --> Completed | Trial completion date: Oct 2025 --> Sep 2024 | Trial primary completion date: May 2025 --> Sep 2024

The APIS ESR1 Mutations Kit demonstrated high sensitivity and specificity as a qualitative qPCR assay for detecting ESR1 mutations in varying WT backgrounds. Its performance with the SensID ESR1 Reference Set 1% AF cfDNA validated the kit's LoD at ≤1% MAF with external samples. The APIS kit is a valuable tool for assessing ESR1 mutations in both clinical and research settings, offering a more accessible alternative to traditional next-generation sequencing (NGS) and dPCR assays.

Determination of IDH1-2 mutation status is important for a variety of malignancies for diagnostics, classification, prognosis, and therapy selection. The Idylla system is easy to use and requires little training; therefore, it is the ideal assay to implement in a variety of labs. Overall, the Idylla platform provides quick, dependable, and easy-to-use technology for performing this analysis.

The Idylla IDH1-2 Mutation Assay Kit performed on the Biocartis Idylla system demonstrated a rapid and cost-effective alternative to the standard approaches. This assay can be used to evaluate clinically relevant IDH variants in a much shorter turnaround time and from limited biological samples, which makes this a preferred technique to develop clinical tests for diagnosis, prognosis, and evaluation of treatment in AML.

We sought to evaluate the genomic and transcriptomic landscapes in primary and metastatic germ cell tumors (GCTs; N = 138) to uncover factors that drive cisplatin resistance...PRA-positive PreC GCTs had significantly lower average PSS scores compared to PRA-negative tumors. Lower PSS scores in chemo-naïve tumors were associated with PRAs, suggesting a potential mechanism for platinum resistance.

In conclusion, employing enrichment techniques for low-allele frequency variants can improve the sensitivity of ESR1 mutation detection in breast cancer. This approach has the potential to enhance our ability to monitor and respond to disease progression dynamically, ultimately supporting more effective, individualized patient care.

A dilution series of DNA fragments, ranging from 5 to 10,000 copies per reaction, was analyzed to determine linearity. The kit's performance was further assessed using the SensID ESR1

For future development, molecular testing will likely include whole genome and transcriptome sequencing, and primarily molecular classifications of myeloid neoplasms have already been suggested. As such, genetically defined groups should still constitute the basis for our understanding of disease development from early onset to progression, while clinicopathological features could then be used to describe the stage of the disease rather than the specific type of myeloid neoplasm.

Our results reveal a significant dysregulation of the B-cell and PC compartments in blood of SM patients, consistent with distinctly altered antibody-isotype profiles in plasma of BMM vs ISM vs ASM patients.

However, staining protocol and scanner type influence accuracy. Larger data sets of scans from different laboratories and scanners may lead to more robust DLMs to identify c-KIT mutations in HE slides.

The final diagnosis was mast cell leukemia. The patient eventually died approximately 1 month after the diagnosis.

P=N/A, N=140, Active, not recruiting, Mayo Clinic | N=200 --> 140

Mohs micrographic surgery or digit-sparing wide local excision has been explored to improve quality of life and replace wide local excision or proximal amputation. AM has a worse prognosis than other subtypes, even in the early stages, indicating its inherent aggressiveness.

The undifferentiated epithelioid morphology and unusual aberrant neuroendocrine marker expression posed significant diagnostic challenges. The major differential diagnoses were discussed in this report.

We highlight novel low-frequency drivers, such as SPHKAP , which correlate with a distinct genomic profile and clinical characteristics. Our study enhances knowledge of this understudied disease and underscores the importance of including samples from diverse ancestries in cancer genomics studies.

55% (42/77) of liquid samples with a KIT -driver mutation had a co-occurring imatinib-resistant alteration, and a minority of cases harbored non- KIT mechanisms of resistance such as FGFR2 fusion, BRAF or EGFR alterations... Known driver and TKI-resistant mutations are identified in liquid biopsies of patients with GIST, with high concordance to tissue in the presence of elevated TF. Liquid biopsy may be valuable in the molecular classification of GIST during the medical management of advanced disease.

In this updated exploratory analysis from INTRIGUE, OS was longer for ripretinib vs sunitinib for pts with KIT exon 11 + 17/18 mutations identified by baseline ctDNA. The safety profile was favorable for pts with KIT exon 11 + 17/18 mutations in the ripretinib arm.

No abstract available

Not achieving complete remission after induction 2 was found to be an independent prognostic factor for OS and EFS. These findings indicate that genetic abnormalities could be considered stratification factors, predict patient outcomes, and imply the application of targeted therapy.

The LASSO-logistic regression model in the study can better predict the risk of PTR. The study includes both PAAs and HLA antibodies, expanding the field of work that has not been involved in the previous prediction model of PTR.

The patients tend to have a high tumor pathological stage and nodal involvement at diagnosis. The high frequency of KRAS exon 2,3,4 mutation and low frequency of BRAF V600E mutations is similar to what has been reported in literature.

Different mutation types of familial GISTs in the same family are very rare, thus it is very important to make the correct diagnosis and treatment strategies according to the results of molecular detection for the management of familial GISTs.

For Pt #1, disease resistance was associated with clonal expansion of minor clones, and 2nd line TKI therapy with gilteritinib provided a proliferative advantage to the clones carrying NRAS and KIT mutations, thereby responsible for relapse. In Pt #2, clonal architecture was less complex, and 1st line TKI therapy with midostaurin was able to eradicate the leukemic clones. Our results corroborate previous findings about clonal selection driven by TKIs, highlighting the importance of a deeper characterization of individual clonal architectures for choosing the best treatment plan for personalized approaches aimed at optimizing outcomes.

Avapritinib was effective for molecular biologically positive CBF-AML patients with KIT mutation after allo-HSCT. The main adverse reaction was myelosuppression, which could generally be tolerated.

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.

Imatinib may be a useful targeted agent for patients with advanced gastric adenocarcinoma who have KIT mutations.

Conclusions The Archer® FUSIONPlex® custom panel detected fusion genes in 10% of driver gene-negative melanomas. Combining DNA- and RNA-based multiplex sequencing is useful to identify potentially targetable gene alterations.

Known under low incidence – mutations require research for 0.4% to 1.1 in pulmonary adenocarcinomas, IDH1/2 inhibitors prescription due to high prevalence of lung carcinoma worldwide. Mutations in IDH1/2 gene may be branching drivers leading to lower subclonality evolution with predictable benefit of IDH1/2 inhibitors.The accumulation of more known cases with IDH1/2 mutations is necessary to elucidate clinicopathological characteristics/clinical evolution after target therapy, in order to reforce the new interpretation of malignant tumours postponed survival through conversion of cell cycle.

This also resulted in significant synergy between BGJ 398 and VEGFR inhibitors (i.e., sunitinib and regorafenib) by enhancing their pro-apoptotic and anti-proliferative activities. Mechanistically, the FGF2-induced activation of the FGFR pathway turns on VEGFR signaling via the overproduction of VEGF-A, induces the interaction between FGFR1/2 and VEGFR1, and thereby renders cancer cells highly sensitive to the dual inhibition of the aforementioned RTKs. Thus, our data uncovers the novel mechanism of the cross-talk between the aforementioned RTKs in IM-resistant GISTs lacking secondary KIT mutations and suggests that the dual blockade of FGFR and VEGFR signaling might be an effective treatment strategy for patients with GIST-acquired IM resistance via KIT-independent mechanisms.