IDH1 R132

The dataset is open for public access and is designed for various applications, from machine learning model training to the exploration of regional and ethnic disease variations. Preliminary validations utilizing Multiple Instance Learning for tasks such as glioma subtype classification and IHC biomarker identification underscore its potential to significantly contribute to global collaboration in brain tumor research, enhancing diagnostic precision and understanding of glioma variability across different populations.

P1, N=81, Completed, Bayer | Active, not recruiting --> Completed

P1/2, N=7, Completed, Servier Bio-Innovation LLC | Active, not recruiting --> Completed | N=92 --> 7 | Trial completion date: Mar 2026 --> Nov 2024 | Trial primary completion date: Mar 2026 --> Nov 2024

A high-throughput screening of 221 anti-cancer drugs identified five candidates-bortezomib, carfilzomib, doxorubicin, panobinostat, and romidepsin-that demonstrated low IC50 values, indicating potential efficacy in treating CS. These findings suggest that NCC-CS1-C1 is a valuable tool for both preclinical and basic research on high-grade conventional central CS.

Positivity for H3K27me3, especially double positivity for H3K27me3 and EZH2, could be a poor prognostic factor for astrocytoma, IDH-mutant. These results suggest the utility of H3K27me3 and EZH2 as candidate markers for estimating the malignancy of astrocytoma, IDH-mutant.

IDH1-mutant CCA is characterized by increased abundance of M2-like TAMs. Targeting CCL2 remodels the tumor immune microenvironment and improves outcomes in preclinical models of IDH1-mutant CCA, highlighting the role for myeloid-targeted immunotherapies in the treatment of this cancer.

Our method achieved a turnaround time of 105 min at the point-of-care from receipt of a tumor biopsy to result with the potential to impact surgical strategy. Our approach can be integrated with recently developed DNA methylation-based diagnostic classification systems, corroborating diagnoses and even further specifying tumor grades, thus enabling a multimodal diagnostic intraoperative assessment of CNS malignancies.

A dual adeno-associated virus split intein system was used to successfully deliver the base editor in vitro and in vivo. Taken together, our study provides a strategy for a precise genetic intervention to target the IDH1 R132H mutation, enabling the development of accurate models to study its impact on glioma biology and serving as a framework for an in vivo gene therapy.

TP53 R248Q mutation increased cell adhesion to various substrates and significantly promoted cell migration on hyaluronic acid and chondroitin sulfate but did not change the migration rates on laminin and collagens IV and I. A double-mutant genotype produced by consequently introducing IDH1 R132H and TP53 R248Q to parental glioblastoma cells was characterized by the highest migration among all the cell lines, with particularly faster motility on chondroitin sulfate. These findings underscore the complex interactions between glioma cells, with the most important driver mutations and specific ECM components regulating cancer cell migration, offering valuable insights for potential therapeutic targets in glioma treatment.

Although the morphological findings and the presence of fusion indicated that the tumor was a cerebellar AG, the DNA methylome profile did not match that of AG. An accumulation of more cases is needed to determine the precise nature of the tumor, which may lead to an expansion of the tumor concept.

This study shows that the incorporation of molecular testing can considerably improve brain tumor diagnoses in Nigeria. Furthermore, this study highlights the diagnostic challenges in resource-limited settings and what is at stake in the global disparities of brain tumor diagnosis.

P2, N=95, Active, not recruiting, Nuvation Bio Inc. | Recruiting --> Active, not recruiting

Among pts with EMP available, 64.2% had intrahepatic cholangiocarcinoma and 69.8% received CT1 (36.1% cisplatinum-gemcitabine). Despite a broader availability of EMP in advanced BTC in recent years, access to TT remains suboptimal even in referral Institutions. Our results demonstrate TT administration as a pivotal positive prognostic factor in a real-world setting, whilst FGFR2 or IDH1 alterations did not act as prognostic determinants per-se. Therefore, strategies aiming at improving the rate of patients receiving TT are warranted.

IDH1/2 mutations are identified in a small subset of NSCLCs. Our findings suggest that >25% of these mutations are hematopoietic in origin with important implications for diagnosis and management of these patients. Among those with mutations arising from the lung neoplasm, IDH1/2 mutations were primarily seen in conjunction with another driver and were subclonal in nature, suggesting patterns of clonal heterogeneity and evolution.

Target-capture NGS provides the opportunity to evaluate many genes in a single assay. Suitability for MRD requires highly uniform and sensitive target enrichment. Our study demonstrated reliable and accurate detection of variants down to 0.05% VAF, providing researchers with the capability to use capture-based NGS for myeloid MRD monitoring.

These mutations are targetable using agents such as ivosidenib and vorasedinib in AML... The Biocartis Idylla IDH1-2 mutation assay shows good concordance with ddPCR and an LOD of 2.5% VAF. Though the analytical sensitivity of this assay is lower than ddPCR, this may not be a limitation in acute, newly diagnosed patients presenting with increased blast counts. This assay offers the advantage of direct specimen testing for PB and BM without DNA extraction with faster turnaround time than other methods.

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.

P2, N=14, Active, not recruiting, National Cancer Institute (NCI) | N=94 --> 14 | Trial completion date: Dec 2024 --> Nov 2025 | Trial primary completion date: Dec 2024 --> Jan 2024

Surgical waste is an important diagnostic resource that should be leveraged for rapid diagnostic sequencing. Sufficient DNA can be easily recovered from surgical waste and sequenced within the same time-frame–but with increased sensitivity–to IHC.

Surgical waste is an important diagnostic resource that should be leveraged for rapid diagnostic sequencing. Sufficient DNA can be easily recovered from surgical waste and sequenced within the same time-frame–but with increased sensitivity–to IHC.

Molecular diagnostics through CGP testing served as an aid in diagnosis according to WHO2021. Cases where drug suggestions were feasible underwent treatment with targeted molecular therapies and checkpoint inhibitor. We experienced cases where hereditary cancer syndromes such as Lynch syndrome were diagnosed through the detection of germline pathogenic variants.

P2, N=20, Recruiting, Washington University School of Medicine | N=15 --> 20 | Trial completion date: Jun 2026 --> Jan 2030 | Trial primary completion date: Jun 2026 --> Jan 2030

P1, N=48, Not yet recruiting, Katy Peters, MD, PhD | Trial completion date: Aug 2027 --> Aug 2029 | Trial primary completion date: Aug 2025 --> Aug 2027

P2, N=145, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jul 2024 --> Jul 2025 | Trial primary completion date: Jul 2024 --> Jul 2025

P2, N=460, Recruiting, Patrick Wen, MD | Trial completion date: Dec 2025 --> Apr 2027 | Trial primary completion date: Mar 2025 --> Feb 2027

The adoption of mutant-specific IDH1 inhibitor molecules could represent a potential panacea for these conditions in the era of targeted therapies. Further studies with larger clinical series are needed to confirm our results and hypothesis.

Our findings provide evidence that IDH1 hotspot mutations serve as driver alterations in this rare yet distinct molecular subset of PCa. Further studies are warranted to correlate response to androgen deprivation and IDH inhibitors.

Validating these insights, biochemical in vitro assays of metabolites produced by mutant vs wild type enzymes were measured and compared. From the results discussed herein, we discuss the mechanistic impact of mutations in IDH1 on its ability to catalyze the formation of αKG and 2HG.

As a consequence, ROS accumulates, lipid peroxidation occurs, and ferroptosis is triggered, thereby promoting acute kidney injury. In summary, this study elucidates a novel mechanism underlying cisplatin-induced nephrotoxicity and provides valuable insights for the development of personalized treatment strategies for tumor patients carrying the IDH1-R132H mutation.

In Phase 2 (100 cases), analysis extended to cfDNA, maintaining high specificity (100 %) with moderate sensitivity (44.2 %). Overall concordance with immunohistochemistry was 61 %, highlighting liquid biopsy's potential in glioma management. The findings emphasized DD-PCR's clinical utility in both tissue and liquid biopsy, underscoring its role in early detection, diagnosis, and therapeutic monitoring of diffuse gliomas.

P3, N=968, Active, not recruiting, Stichting Hemato-Oncologie voor Volwassenen Nederland | Recruiting --> Active, not recruiting | Trial completion date: May 2034 --> Sep 2034 | Trial primary completion date: Oct 2024 --> Apr 2027

To our knowledge, this is the first report describing the development of a matched pair of 3D patient-derived cell models representative of MT and temozolomide (TMZ)-induced hypermutator phenotype (HMP) in IDH-mutant glioma, providing insights into genetic and metabolic changes during MT/HMP. This novel in vitro model allows further investigation of the mechanisms of MT at the cellular level.

The Idyllaâ„¢ IDH1-2 Mutation Assay demonstrates high sensitivity and specificity in detecting IDH1-2 mutations in gliomas across real-world clinical settings. The rate of development of targeted treatments and biomarkers has led to increased demand for rapid results in the clinical diagnostic laboratory. This system is easily integrated into pathology laboratories, facilitating fast turnaround time of IDH1-2 results to clinicians.

P2, N=15, Recruiting, Washington University School of Medicine | Trial completion date: Aug 2025 --> Jun 2026 | Trial primary completion date: Aug 2025 --> Jun 2026

P1, N=72, Recruiting, Institut de Recherches Internationales Servier | Trial primary completion date: Mar 2024 --> Feb 2025

This active site remodeling reveals a possible mechanism of resistance to selective mutant IDH1 therapeutic inhibitors. This work enhances our understanding of fundamental IDH1 mechanisms while pinpointing regions for improving inhibitor selectivity.

P1, N=8, Terminated, Academic and Community Cancer Research United | Trial completion date: Jul 2025 --> Dec 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Jan 2025 --> Dec 2023; Low accrual

Significantly, compound 23h has the ability to cross the blood-brain barrier (B/P ratio, 0.76) and demonstrates remarkable in vivo antitumor efficacy (20 mg/kg) in the U87 MG-IDH1R132H orthotopic transplantation mouse models without any notable toxicity. This proof-of-concept investigation substantiates the viability of discovering small molecules that concurrently target mIDH1 and NAMPT, providing valuable leads for the treatment of glioma and an efficient approach for the discovery of multitarget antitumor drugs.

The clinical value of IDH and ATRX mutations in prognostic assessment was confirmed (p ≤0.05). The overexpression of p53 had no significant impact on OS (p = 0.726). Therefore, p53 alone cannot predict survival in glioblastoma patients. Based on the results, these biomarkers may be a potential therapeutic target to prolong patient survival, hence the need for further investigations.

The pH-based colorimetric indicator of LNA-LAMP facilitates convenient visual interpretation of reactions, and we demonstrate successful translation to an end-point format using absorbance ratio, allowing for an alternative and objective approach for differentiating between positive and negative reactions. Importantly, the LNA-LAMP genotyping panel is highly reproducible, with no false-positive or false-negative results observed.

Significant differences in GA and immune biomarkers are noted between IDH1/2+ and IDHwt iCCA. IDH1-/2-mutated tumors appear immunologically cold without gLOH. These immunogenomic data provide insight for precision targeting of iCCA with IDH alterations.

Importantly, pharmacological blockage of DNA methylation or IDH1-R132H mutant and CD47/SIRPα signaling synergistically enhances TAM-based phagocytosis and glioma elimination in vivo. Our findings unveil a general mechanism by which NSUN5/TET2/RBFOX2 signaling regulates RNA metabolism and highlight NSUN5 targeting as a potential strategy for glioma immune therapy.