scholarly journals MIAmS: microsatellite instability detection on NGS amplicons data

2019 ◽  
Author(s):  
Frédéric Escudié ◽  
Charles Van Goethem ◽  
David Grand ◽  
Julie Vendrell ◽  
Anna Vigier ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Length Distribution ◽  
Supplementary Information ◽  
Distribution Analysis ◽  
Dna Mismatch ◽  
Repair Deficiency ◽  
Paired Normal Tissue ◽  
Next Generation Sequencing Ngs ◽  
User Friendly ◽  
Tumor Genome

Abstract Summary Microsatellite instability (MSI) is a molecular marker of DNA mismatch repair deficiency frequently at play in oncogenesis. MSI testing is used for diagnostic, prognostic and therapeutic purposes in several cancers. The current gold standard analysis for microsatellite status is based on length distribution analysis of multiplex-PCR generated DNA fragments from tumor samples which is a laborious and time consuming method. Next generation sequencing (NGS) using amplicon panels is an easy, accurate and scalable technique to determine both the microsatellite status and tumor genome mutations at the same time. Here, we describe MIAmS, an application designed to tag microsatellite status from amplicon NGS of tumor samples. Interestingly, this tool does not require paired normal tissue for comparison. In addition, this scalable application provides a user-friendly report for the interpretation of the results by biologists and exhibits a strong accuracy and robustness for determination of the MSI status. Availability and implementation https://github.com/bialimed/miams. Evaluation data are available at http://www.ebi.ac.uk/ena/data/view/PRJEB31725. Contact [email protected] Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Immunohistochemistry Versus Microsatellite Instability Testing in Phenotyping Colorectal Tumors

2002 ◽  
Vol 20 (4) ◽  
pp. 1043-1048 ◽  
Author(s):  
Noralane M. Lindor ◽  
Lawrence J. Burgart ◽  
Olga Leontovich ◽  
Richard M. Goldberg ◽  
Julie M. Cunningham ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Predictive Value ◽  
Dna Mismatch Repair ◽  
Cost Effective ◽  
Colorectal Tumors ◽  
Dna Mismatch ◽  
Testing Strategies ◽  
Repair Deficiency ◽  
Dna Mismatch Repair Deficiency

PURPOSE: To compare microsatellite instability (MSI) testing with immunohistochemical (IHC) detection of hMLH1 and hMSH2 in colorectal cancer. PATIENTS AND METHODS: Colorectal cancers from 1,144 patients were assessed for DNA mismatch repair deficiency by two methods: MSI testing and IHC detection of hMLH1 and hMSH2 gene products. High-frequency MSI (MSI-H) was defined as more than 30% instability of at least five markers; low-level MSI (MSI-L) was defined as 1% to 29% of loci unstable. RESULTS: Of 1,144 tumors tested, 818 showed intact expression of hMLH1 and hMSH2. Of these, 680 were microsatellite stable (MSS), 27 were MSI-H, and 111 were MSI-L. In all, 228 tumors showed absence of hMLH1 expression and 98 showed absence of hMSH2 expression: all were MSI-H. CONCLUSION: IHC in colorectal tumors for protein products hMLH1 and hMSH2 provides a rapid, cost-effective, sensitive (92.3%), and extremely specific (100%) method for screening for DNA mismatch repair defects. The predictive value of normal IHC for an MSS/MSI-L phenotype was 96.7%, and the predictive value of abnormal IHC was 100% for an MSI-H phenotype. Testing strategies must take into account acceptability of missing some cases of MSI-H tumors if only IHC is performed.

scholarly journals EpiGraph: an open-source platform to quantify epithelial organization

2019 ◽  
Author(s):  
Pablo Vicente-Munuera ◽  
Pedro Gómez-Gálvez ◽  
Robert J Tetley ◽  
Cristina Forja ◽  
Antonio Tagua ◽  
...  
Keyword(s):  
Image Analysis ◽  
Open Access ◽  
Supplementary Information ◽  
Analysis Tool ◽  
Distribution Analysis ◽  
Supplementary Data ◽  
Programming Skills ◽  
User Friendly ◽  
Degree Of Order

Abstract Summary Here we present EpiGraph, an image analysis tool that quantifies epithelial organization. Our method combines computational geometry and graph theory to measure the degree of order of any packed tissue. EpiGraph goes beyond the traditional polygon distribution analysis, capturing other organizational traits that improve the characterization of epithelia. EpiGraph can objectively compare the rearrangements of epithelial cells during development and homeostasis to quantify how the global ensemble is affected. Importantly, it has been implemented in the open-access platform Fiji. This makes EpiGraph very user friendly, with no programming skills required. Availability and implementation EpiGraph is available at https://imagej.net/EpiGraph and the code is accessible (https://github.com/ComplexOrganizationOfLivingMatter/Epigraph) under GPLv3 license. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Real-world Concordance in Microsatellite Instability Status Between PCR-based Testing and Next-Generation Sequencing Assay for Solid Tumors

2021 ◽  
Author(s):  
Keitaro Shimozaki ◽  
Hideyuki Hayashi ◽  
Sara Horie ◽  
Akihiko Chida ◽  
Kai Tsugaru ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Microsatellite Instability ◽  
Solid Tumors ◽  
Real World ◽  
Next Generation ◽  
Predictive Values ◽  
Primary Endpoints ◽  
Repair Deficiency ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Abstract Background: Various malignancies exhibit high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR). The MSI-IVD kit, which can detect MSI status using a polymerase chain reaction (PCR)-based method, was approved as the first tumor-agnostic companion diagnostic for pembrolizumab in patients with MSI-H solid tumors in Japan. Recently, next-generation sequencing (NGS), which can also detect MSI-H/dMMR, has been made clinically available. However, the real-world concordance in MSI-H/dMMR between the PCR-based testing and NGS is yet to be thoroughly investigated.Methods: A retrospective study was conducted to evaluate the utility of MSI testing using PCR-based testing and NGS assay in patients eligible for both MSI testing and any NGS platform. Co-primary endpoints included positive and negative predictive values of MSI-H/dMMR.Results: Between December 2018 and June 2020, 40 patients underwent both PCR-based MSI testing and NGS assay for MSI. Two patients with gastric neuroendocrine carcinoma and ovarian cancer were confirmed to have MSI-H/dMMR in both examinations. Among the 38 patients diagnosed as microsatellite stable by PCR-based testing, 2 (5.2%) with pancreatic cancer were diagnosed as MSI-H after NGS analyses. NGS had positive and negative predictive values of 100% (2/2) and 94.7% (36/38), respectively, for MSI-H, while the concordance between NGS and PCR-based testing was 94.9% (38/40).Conclusion: Similar to PCR-based MSI testing, NGS can be useful for evaluating MSI/MMR status in clinical practice and could be an important alternative method for detecting MSI-H/dMMR in the future.

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