DNA Mismatch Repair Deficiency Detection in Colorectal Cancer by a New Microsatellite Instability Analysis System

Wu, Shafei; Liu, Xiaoding; Wang, Jing; Zhou, Weixun; Guan, Mei; Liu, Yuanyuan; Pang, Junyi; Lü, Tao; Zhou, Liangrui; Shi, Xiaohua; Wu, Huanwen; Liang, Zhiyong; Zhang, Xuan

doi:10.1007/s12539-020-00358-8

Cited by 19 publications

(16 citation statements)

References 18 publications

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“…Emerging PCR-based assays differ from the standard reference PCR method by the nature and number of targeted MS markers and/or the read-out strategy of PCR products ( Table 2 ). For example, some groups integrated the analysis of novel long mononucleotide repeats (LMR) besides the traditional pentaplex panel [ 58 , 59 ]. Bacher et al identified a large number of mononucleotide repeats with increased repeat length (40–60 bp) compared to the MS markers traditionally used for MSI testing [ 59 ].…”

Section: Other Msi Approaches On Tumour Tissue Samplesmentioning

confidence: 99%

“…Thus, the analysis of LMR markers allowed to enhance the detection sensitivity of the MSI-PCR assay. The commercial LMR MSI analysis system (Promega ® , Madison, WI, USA) that includes four conventional mononucleotide MS markers ( BAT25 , BAT26 , Mono27 , NR21 , and NR24 ) and 4 LMR markers ( BAT-52 , BAT-56 , BAT-59 and BAT-60 ) notably reached a higher agreement with IHC in colorectal samples compared to the Promega ® MSI analysis system [ 58 ]. The utility of such panel still needs to be confirmed for non-colorectal specimens.…”

Section: Other Msi Approaches On Tumour Tissue Samplesmentioning

confidence: 99%

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Detection of Microsatellite Instability: State of the Art and Future Applications in Circulating Tumour DNA (ctDNA)

Gilson

Merlin

Harlé

2021

Cancers

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Microsatellite instability (MSI) is a molecular scar resulting from a defective mismatch repair system (dMMR) and associated with various malignancies. MSI tumours are characterized by the accumulation of mutations throughout the genome and particularly clustered in highly repetitive microsatellite (MS) regions. MSI/dMMR status is routinely assessed in solid tumours for the initial screening of Lynch syndrome, the evaluation of cancer prognosis, and treatment decision-making. Currently, pentaplex PCR-based methods and MMR immunohistochemistry on tumour tissue samples are the standard diagnostic methods for MSI/dMMR. Other tissue methods such as next-generation sequencing or real-time PCR-based systems have emerged and represent viable alternatives to standard MSI testing in specific settings. The evolution of the standard molecular techniques has offered the opportunity to extend MSI determination to liquid biopsy based on the analysis of cell-free DNA (cfDNA) in plasma. This review aims at synthetizing the standard and emerging techniques used on tumour tissue samples for MSI/dMMR determination. We also provide insights into the MSI molecular techniques compatible with liquid biopsy and the potential clinical consequences for patients with solid cancers.

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Section: Other Msi Approaches On Tumour Tissue Samplesmentioning

confidence: 99%

Section: Other Msi Approaches On Tumour Tissue Samplesmentioning

confidence: 99%

Detection of Microsatellite Instability: State of the Art and Future Applications in Circulating Tumour DNA (ctDNA)

Gilson

Merlin

Harlé

2021

Cancers

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“…Low or loss of MLH1 and PMS2 protein expression might often occur in TNBC patients based on our results and the published data available. Low-expressed PMS2 protein was also observed in one out of 10 cases of colorectal cancer in our previous study cohort, and other MMR proteins were all highly expressed in all samples (data not shown) ( 26 ). The potential biological implications of this process remain to be explored further.…”

Section: Discussionmentioning

confidence: 69%

“…The sample was considered to be microsatellite unstable if there was a shift of three base pairs in the tumor allele compared with normal tissue. MSI-H, MSI-L (low-frequency microsatellite instability), and MSS were distinguished when two or more, one, and no unstable markers were observed, respectively ( 26 ).…”

Section: Methodsmentioning

confidence: 99%

Triple-Negative Breast Cancer: Intact Mismatch Repair and Partial Co-Expression of PD-L1 and LAG-3

Shi

Wang

et al. 2021

Front. Immunol.

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Background and AimPoor response to immune checkpoint inhibitors (ICIs) has been observed in most triple-negative breast cancer (TNBC) cases (around 80%). Our aim was to investigate the status of mismatch repair (MMR), microsatellite instability (MSI), programmed death-ligand 1 (PD-L1), and lymphocyte-activation gene 3 (LAG-3) in TNBC.MethodsA total of 74 TNBC samples were retrospectively analyzed. MMR and MSI were evaluated by immunohistochemistry (IHC) and polymerase chain reaction (PCR) using Promega 1.2 and NCI panels, respectively. PD-L1, LAG-3, and CD8 expression was assessed by IHC.ResultsNone of the cases demonstrated deficient MMR (dMMR) or MSI. In total, 43/74 cases (58.1%) were PD-L1+, including 1 tumor PD-L1+, 25 tumor-infiltrating lymphocytes (TILs) PD-L1+, and 17 cases involving concurrence of tumor and TIL PD-L1+. The rate of TIL PD-L1+ was remarkably higher than that of tumor PD-L1+ (P<0.001). We identified 20 LAG-3+ cases (27.0%, 20/74), all of which were PD-L1+. Co-expression of PD-L1 and LAG-3 was noted in 46.5% (20/43) of the PD-L1+ population. In the LAG-3+ subtype (co-expression of PD-L1 and LAG-3), high correlation between TILs PD-L1+ and LAG-3+ was observed (P<0.01). A high frequency of CD8+ (98.6%, 73/74) was observed.ConclusiondMMR/MSI characteristics may not be a practical predictive marker for ICIs in TNBC. PD-L1+ is more common in TILs than in tumors. In the PD-L1+ population, approximately half of the cases showed LAG-3 co-expression. For patients with a poor response to PD-1(L1) mono ICI, dual blockade of PD-1(L1) and LAG-3 may be a viable option for the management of TNBC.

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“…Primers were designed for mouse microsatellite loci L24372-A27, U12235-A24, mBat30, mBat37, mBat64, and mBat67 on mouse build GRCm38.p6 [37][38][39][40][41][42]. All primers were ordered as stated in Table S2 (Integrated DNA Technologies, Coralville, IA, USA) and amplified with Platinum™ SuperFi™ PCR Master Mix (12.5 µL; Thermo Fisher Scientific, Waltham, MA, USA) with kit-provided GC Enhancer (5 µL), with the exception of mBat67, where molecular grade water (5 µL) was substituted in place of GC Enhancer.…”

Section: Fragment Analysis and Sanger Sequencing To Assess Microsatel...mentioning

confidence: 99%

Mesothelioma Mouse Models with Mixed Genomic States of Chromosome and Microsatellite Instability

Baxter

Dai

Sanders

et al. 2022

Cancers

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Malignant mesothelioma (MMe) is a rare malignancy originating from the linings of the pleural, peritoneal and pericardial cavities. The best-defined risk factor is exposure to carcinogenic mineral fibers (e.g., asbestos). Genomic studies have revealed that the most frequent genetic lesions in human MMe are mutations in tumor suppressor genes. Several genetically engineered mouse models have been generated by introducing the same genetic lesions found in human MMe. However, most of these models require specialized breeding facilities and long-term exposure of mice to asbestos for MMe development. Thus, an alternative model with high tumor penetrance without asbestos is urgently needed. We characterized an orthotopic model using MMe cells derived from Cdkn2a+/−;Nf2+/− mice chronically injected with asbestos. These MMe cells were tumorigenic upon intraperitoneal injection. Moreover, MMe cells showed mixed chromosome and microsatellite instability, supporting the notion that genomic instability is relevant in MMe pathogenesis. In addition, microsatellite markers were detectable in the plasma of tumor-bearing mice, indicating a potential use for early cancer detection and monitoring the effects of interventions. This orthotopic model with rapid development of MMe without asbestos exposure represents genomic instability and specific molecular targets for therapeutic or preventive interventions to enable preclinical proof of concept for the intervention in an immunocompetent setting.

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DNA Mismatch Repair Deficiency Detection in Colorectal Cancer by a New Microsatellite Instability Analysis System

Cited by 19 publications

References 18 publications

Detection of Microsatellite Instability: State of the Art and Future Applications in Circulating Tumour DNA (ctDNA)

Detection of Microsatellite Instability: State of the Art and Future Applications in Circulating Tumour DNA (ctDNA)

Triple-Negative Breast Cancer: Intact Mismatch Repair and Partial Co-Expression of PD-L1 and LAG-3

Mesothelioma Mouse Models with Mixed Genomic States of Chromosome and Microsatellite Instability

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