Next-Generation Sequencing Panel for 1p/19q Codeletion and IDH1-IDH2 Mutational Analysis Uncovers Mistaken Overdiagnoses of 1p/19q Codeletion by FISH

Biase, Dario de; Acquaviva, Giorgia; Visani, Michela; Marucci, Gianluca; Leo, Antonio De; Maloberti, Thais; Sanza, Viviana; Oto, Enrico Di; Franceschi, Enrico; Mura, Antonella; Ragazzi, Moira; Serra, Silvia; Froio, Elisabetta; Bisagni, Alessandra; Brandes, Alba Ariela; Pession, Annalisa; Tallini, Giovanni

doi:10.1016/j.jmoldx.2021.06.004

Cited by 11 publications

(5 citation statements)

References 28 publications

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“…It necessitates a high labor input and additional resources, such as a separate dark room to conduct fluorescence experiments, special equipment, solution, and reagents 15 . Moreover, the time-consuming nature of interpretation and analysis, coupled with considerable variability in FISH results on 1p/19q status, further complicates its use in clinical practice 12 , 14 , 37 . It is possibly introduced by an unavoidable bias due to the random selection of tumor cells, which can reduce diagnostic accuracy, especially in heterogeneous cases with a high proportion of non-tumor cells 38 .…”

Section: Discussionmentioning

confidence: 99%

Efficient diagnosis of IDH-mutant gliomas: 1p/19qNET assesses 1p/19q codeletion status using weakly-supervised learning

Kim,

Lee,

Ahn

et al. 2023

npj Precis. Onc.

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Accurate identification of molecular alterations in gliomas is crucial for their diagnosis and treatment. Although, fluorescence in situ hybridization (FISH) allows for the observation of diverse and heterogeneous alterations, it is inherently time-consuming and challenging due to the limitations of the molecular method. Here, we report the development of 1p/19qNET, an advanced deep-learning network designed to predict fold change values of 1p and 19q chromosomes and classify isocitrate dehydrogenase (IDH)-mutant gliomas from whole-slide images. We trained 1p/19qNET on next-generation sequencing data from a discovery set (DS) of 288 patients and utilized a weakly-supervised approach with slide-level labels to reduce bias and workload. We then performed validation on an independent validation set (IVS) comprising 385 samples from The Cancer Genome Atlas, a comprehensive cancer genomics resource. 1p/19qNET outperformed traditional FISH, achieving R2 values of 0.589 and 0.547 for the 1p and 19q arms, respectively. As an IDH-mutant glioma classifier, 1p/19qNET attained AUCs of 0.930 and 0.837 in the DS and IVS, respectively. The weakly-supervised nature of 1p/19qNET provides explainable heatmaps for the results. This study demonstrates the successful use of deep learning for precise determination of 1p/19q codeletion status and classification of IDH-mutant gliomas as astrocytoma or oligodendroglioma. 1p/19qNET offers comparable results to FISH and provides informative spatial information. This approach has broader applications in tumor classification.

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Section: Discussionmentioning

confidence: 99%

Efficient diagnosis of IDH-mutant gliomas: 1p/19qNET assesses 1p/19q codeletion status using weakly-supervised learning

Kim,

Lee,

Ahn

et al. 2023

npj Precis. Onc.

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show abstract

“…In routine pathological analysis of gliomas, fluorescence in situ hybridization and next-generation sequencing are commonly used to detect 1p/19q codeletion. 108,109) We attempted to identify the metabolite changes associated with 1p/19q codeletion using global metabolomics (G-Met) analysis. Our goal was to develop a quantitative molecular diagnostic method based on these findings.…”

Section: Structure and Diagnostic Performance Of Blood Biomarkers For...mentioning

confidence: 99%

Analysis of Metabolic Changes in Endogenous Metabolites and Diagnostic Biomarkers for Various Diseases Using Liquid Chromatography and Mass Spectrometry

Maekawa

2024

Biological & Pharmaceutical Bulletin

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Analysis of endogenous metabolites in various diseases is useful for searching diagnostic biomarkers and elucidating the molecular mechanisms of pathophysiology. The author and collaborators have developed some LC/tandem mass spectrometry (LC/MS/MS) methods for metabolites and applied them to disease-related samples. First, we identified urinary conjugated cholesterol metabolites and serum N-palmitoyl-O-phosphocholine serine as useful biomarkers for Niemann-Pick disease type C (NPC). For the purpose of intraoperative diagnosis of glioma patients, we developed the LC/MS/MS analysis methods for 2-hydroxyglutaric acid or cystine and found that they could be good differential biomarkers. For renal cell carcinoma, we searched for various biomarkers for early diagnosis, malignancy evaluation and recurrence prediction by global metabolome analysis and targeted LC/MS/MS analysis. In pathological analysis, we developed a simultaneous LC/MS/MS analysis method for 13 steroid hormones and applied it to NPC cells, we found 6 types of reductions in NPC model cells. For non-alcoholic steatohepatitis (NASH), model mice were prepared with special diet and plasma bile acids were measured, and as a result, hydrophilic bile acids were significantly increased. In addition, we developed an LC/MS/MS method for 17 sterols and analyzed liver cholesterol metabolites and found a decrease in phytosterols and cholesterol synthetic markers and an increase in non-enzymatic oxidative sterols in the pre-onset stage of NASH. We will continue to challenge themselves to add value to clinical practice based on cutting-edge analytical chemistry methodology.

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“…For diagnosing IDH-mutant, 1p/19q-codeleted tumors, a critical hallmark is the presence of whole-arm 1p/19q codeletion which can be investigated by multiple assays and FISH is commonly used [ 44 ]. However, due to the limited targeting of single loci by the FISH probes, false positive results are possible, especially in presence of tumors with complex karyotypes [ 45 , 46 ]. In many cases, this occurrence is due to presence of partial deletions which are detected by FISH but are not biologically or diagnostically relevant.…”

Section: Applying Molecular Assays To the Diagnostic Workup Of Cns Tu...mentioning

confidence: 99%

Molecular neuropathology: an essential and evolving toolbox for the diagnosis and clinical management of central nervous system tumors

Bertero,

Mangherini,

Ricci

et al. 2023

Virchows Arch

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Molecular profiling has transformed the diagnostic workflow of CNS tumors during the last years. The latest WHO classification of CNS tumors (5th edition), published in 2021, pushed forward the integration between histopathological features and molecular hallmarks to achieve reproducible and clinically relevant diagnoses. To address these demands, pathologists have to appropriately deal with multiple molecular assays mainly including DNA methylation profiling and DNA/RNA next generation sequencing. Tumor classification by DNA methylation profiling is now a critical tool for many diagnostic tasks in neuropathology including the assessment of complex cases, to evaluate novel tumor types and to perform tumor subgrouping in hetereogenous entities like medulloblastoma or ependymoma. DNA/RNA NGS allow the detection of multiple molecular alterations including single nucleotide variations, small insertions/deletions (InDel), and gene fusions. These molecular markers can provide key insights for diagnosis, for example, if a tumor-specific mutation is detected, but also for treatment since targeted therapies are progressively entering the clinical practice. In the present review, a brief, but comprehensive overview of these tools will be provided, discussing their technical specifications, diagnostic value, and potential limitations. Moreover, the importance of molecular profiling will be shown in a representative series of CNS neoplasms including both the most frequent tumor types and other selected entities for which molecular characterization plays a critical role.

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Next-Generation Sequencing Panel for 1p/19q Codeletion and IDH1-IDH2 Mutational Analysis Uncovers Mistaken Overdiagnoses of 1p/19q Codeletion by FISH

Cited by 11 publications

References 28 publications

Efficient diagnosis of IDH-mutant gliomas: 1p/19qNET assesses 1p/19q codeletion status using weakly-supervised learning

Efficient diagnosis of IDH-mutant gliomas: 1p/19qNET assesses 1p/19q codeletion status using weakly-supervised learning

Analysis of Metabolic Changes in Endogenous Metabolites and Diagnostic Biomarkers for Various Diseases Using Liquid Chromatography and Mass Spectrometry

Molecular neuropathology: an essential and evolving toolbox for the diagnosis and clinical management of central nervous system tumors

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