ArticleClinical chemistry2018
Accurate Pan-Cancer Molecular Diagnosis of Microsatellite Instability by Single-Molecule Molecular Inversion Probe Capture and High-Throughput Sequencing.
Article in Clinical chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 70 citations in OpenAlex.
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- Analysis of Concordance Between Next-Generation Sequencing Assessment of Microsatellite Instability and Immunohistochemistry-Mismatch Repair From Solid Tumors.JCO precision oncology · 2024Article
- Oncological characteristics, treatments and prognostic outcomes in MMR-deficient colorectal cancer.Biomarker research · 2024Review
- Construction and Validation of a Prognostic Risk Prediction Model for Lactate Metabolism-Related lncRNA in Endometrial Cancer.Biochemical genetics · 2024Article
- Detecting Microsatellite Instability in Endometrial, Colon, and Stomach Cancers Using Targeted NGS.Cancers · 2023Article
- Chimeras in Merlot grapevine revealed by phased assembly.BMC genomics · 2023Article
- Discrepancy among microsatellite instability detection methodologies in non-colorectal cancer: Report of 3 cases.World journal of clinical cases · 2023Article
- Microsatellite instability assessment is instrumental for Predictive, Preventive and Personalised Medicine: status quo and outlook.The EPMA journal · 2023Review
- Development of molecular inversion probes for soybean progeny genomic selection genotyping.The plant genome · 2023Article
- Clinicopathological and molecular analysis of microsatellite instability in prostate cancer: a multi-institutional study in China.Frontiers in oncology · 2023Article
- LT-RPA: An Isothermal DNA Amplification Approach for Improved Microsatellite Genotyping and Microsatellite Instability Detection.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Clinical prospects of WRN inhibition as a treatment for MSI tumours.NPJ precision oncology · 2022Review
- Evaluating morphological features for predicting microsatellite instability status in colorectal cancer.Medical journal, Armed Forces India · 2022Article
- Prediction of immunotherapy efficacy and immunomodulatory role of hypoxia in colorectal cancer.Therapeutic advances in medical oncology · 2022Review
- Assessment of Microsatellite Instability from Next-Generation Sequencing Data.Advances in experimental medicine and biology · 2022Article
- Review
- PD-L1 Expression Is Significantly Associated with Tumor Mutation Burden and Microsatellite Instability Score.Cancers · 2021Article
- Profiling diverse sequence tandem repeats in colorectal cancer reveals co-occurrence of microsatellite and chromosomal instability involving Chromosome 8.Genome medicine · 2021Article
- Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMicrosatellite instability (MSI) is an emerging actionable phenotype in oncology that informs tumor response to immune checkpoint pathway immunotherapy. However, there remains a need for MSI diagnostics that are low cost, highly accurate, and generalizable across cancer types. We developed a method for targeted high-throughput sequencing of numerous microsatellite loci with pan-cancer informativity for MSI using single-molecule molecular inversion probes (smMIPs).
methodsWe designed a smMIP panel targeting 111 loci highly informative for MSI across cancers. We developed an analytical framework taking advantage of smMIP-mediated error correction to specifically and sensitively detect instability events without the need for typing matched normal material.
resultsUsing synthetic DNA mixtures, smMIPs were sensitive to at least 1% MSI-positive cells and were highly consistent across replicates. The fraction of identified unstable microsatellites discriminated tumors exhibiting MSI from those lacking MSI with high accuracy across colorectal (100% diagnostic sensitivity and specificity), prostate (100% diagnostic sensitivity and specificity), and endometrial cancers (95.8% diagnostic sensitivity and 100% specificity). MSI-PCR, the current standard-of-care molecular diagnostic for MSI, proved equally robust for colorectal tumors but evidenced multiple false-negative results in prostate (81.8% diagnostic sensitivity and 100% specificity) and endometrial (75.0% diagnostic sensitivity and 100% specificity) tumors.
conclusionssmMIP capture provides an accurate, diagnostically sensitive, and economical means to diagnose MSI across cancer types without reliance on patient-matched normal material. The assay is readily scalable to large numbers of clinical samples, enables automated and quantitative analysis of microsatellite instability, and is readily standardized across clinical laboratories.
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