scholarly journals Immune Checkpoint Inhibition in Metastatic Colorectal Cancer Harboring Microsatellite Instability or Mismatch Repair Deficiency

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1149
Author(s):  
Romain Cohen ◽  
Raphaël Colle ◽  
Thomas Pudlarz ◽  
Maximilien Heran ◽  
Alex Duval ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Predictive Biomarker ◽  
Repair System ◽  
Comprehensive Overview ◽  
Dna Mismatch ◽  
Dna Mismatch Repair System ◽  
Metastatic Setting ◽  
Future Challenges ◽  
Tumor Mutational Burden

Microsatellite instability (MSI) is a tumor phenotype related to a deficient DNA mismatch repair system (dMMR). This phenotype, observed in 5% of metastatic mCRC but 10–18% of localized CRC, is associated with high tumor mutational burden with highly immunogenic neoantigens. It has emerged as a major predictive biomarker for the efficacy of ICIs. In this review, we will present a comprehensive overview of the literature concerning the efficacy of ICIs in MSI/dMMR mCRC, with a focus on new developments in first-line metastatic setting. Then, we will present current and future challenges of immuno-oncology for patients with MSI/dMMR metastatic CRC.

Warthin Tumors Do Not Have Microsatellite Instability and Express Normal DNA Mismatch Repair Proteins

2006 ◽  
Vol 130 (1) ◽  
pp. 52-56 ◽  
Author(s):  
Jennifer L. Hunt
Keyword(s):  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
Repair System ◽  
Dna Mismatch ◽  
Epithelial Component ◽  
Repair Enzymes ◽  
Dna Mismatch Repair System ◽  
Mismatch Repair System ◽  
Polymerase Chain

Abstract Context.—Warthin tumors are controversial entities with a poorly understood etiology. Although some investigators have suggested a neoplastic origin, others have supported a developmental anomaly. A recent study described the absence of staining for hMLH1 and hMSH2 proteins in the epithelial component of Warthin tumors, suggesting that they arise secondary to defects in the DNA mismatch repair system. Objective.—To determine if Warthin tumors exhibit evidence of DNA mismatch repair defects. Design.—Immunostains for hMLH1 and hMSH2 were performed using a standard approach. Microdissection of the epithelial component was followed by DNA extraction from the tissue fragments. Polymerase chain reaction and capillary electrophoresis analyses were performed for the following 5 National Cancer Institute–recommended microsatellites: D2s123, D5s346, D17s250, BAT25, and BAT26. Patients.—Twelve patients with Warthin tumors were included. Results.—The immunostains for hMLH1 and hMSH2 showed preserved expression in the nuclei of the epithelial component of all Warthin tumors. No microsatellite instability was detected, and no loss of heterozygosity was seen. Conclusions.—These results are not concordant with previously reported results showing loss of expression of the hMLH1 and hMSH2 DNA mismatch repair enzymes in the epithelial component of Warthin tumors. Furthermore, no microsatellite instability was detected in the 5 loci tested for each tumor in this series. These data demonstrate that Warthin tumors do not have evidence of DNA mismatch repair defects at the genomic or protein expression level.

Oxidative stress induces inactivation of the DNA mismatch repair system and causes microsatellite instability

2000 ◽  
Vol 118 (4) ◽  
pp. A707
Author(s):  
Christoph Gasche ◽  
Christina L. Chang ◽  
Jennifer Rhees ◽  
Ajay Goel ◽  
Luigi Ricciardiello ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
Repair System ◽  
Dna Mismatch ◽  
Dna Mismatch Repair System ◽  
Mismatch Repair System

Functional Specifics of the MutL Protein of the DNA Mismatch Repair System in Different Organisms

2020 ◽  
Vol 46 (6) ◽  
pp. 875-890
Author(s):  
M. V. Monakhova ◽  
M. A. Milakina ◽  
R. M. Trikin ◽  
T. S. Oretskaya ◽  
E. A. Kubareva
Keyword(s):  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
Repair System ◽  
Dna Mismatch ◽  
Dna Mismatch Repair System ◽  
Mismatch Repair System

scholarly journals Steady-state regulation of the human DNA mismatch repair system.

2000 ◽  
Vol 275 (37) ◽  
pp. 29178
Author(s):  
Dong Kyung Chang ◽  
Luigi Ricciardiello ◽  
Ajay Goel ◽  
Christina L. Chang ◽  
C. Richard Boland
Keyword(s):  
Steady State ◽  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
State Regulation ◽  
Repair System ◽  
Dna Mismatch ◽  
Human Dna ◽  
Dna Mismatch Repair System ◽  
Mismatch Repair System

Oxidative stress inactivates the human DNA mismatch repair system

2002 ◽  
Vol 283 (1) ◽  
pp. C148-C154 ◽  
Author(s):  
Christina L. Chang ◽  
Giancarlo Marra ◽  
Dharam P. Chauhan ◽  
Hannah T. Ha ◽  
Dong K. Chang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mismatch Repair ◽  
Chronic Inflammation ◽  
Dna Mismatch Repair ◽  
Repair System ◽  
Dna Microsatellites ◽  
Single Base ◽  
Dna Mismatch ◽  
Human Dna ◽  
Dna Mismatch Repair System

In the human DNA mismatch repair (MMR) system, hMSH2 forms the hMutSα and hMutSβ complexes with hMSH6 and hMSH3, respectively, whereas hMLH1 and hPMS2 form the hMutLα heterodimer. These complexes, together with other components in the MMR system, correct single-base mismatches and small insertion/deletion loops that occur during DNA replication. Microsatellite instability (MSI) occurs when the loops in DNA microsatellites are not corrected because of a malfunctioning MMR system. Low-frequency MSI (MSI-L) is seen in some chronically inflamed tissues in the absence of genetic inactivation of the MMR system. We hypothesize that oxidative stress associated with chronic inflammation might damage protein components of the MMR system, leading to its functional inactivation. In this study, we demonstrate that noncytotoxic levels of H2O2 inactivate both single-base mismatch and loop repair activities of the MMR system in a dose-dependent fashion. On the basis of in vitro complementation assays using recombinant MMR proteins, we show that this inactivation is most likely due to oxidative damage to hMutSα, hMutSβ, and hMutLα protein complexes. We speculate that inactivation of the MMR function in response to oxidative stress may be responsible for the MSI-L seen in nonneoplastic and cancer tissues associated with chronic inflammation.

scholarly journals Endometrial cancer and microsatellite instability status

Open Medicine ◽  
2014 ◽  
Vol 10 (1) ◽  
Author(s):  
Daiva Kanopiene ◽  
Jolanta Vidugiriene ◽  
Konstantinas Povilas Valuckas ◽  
Giedre Smailyte ◽  
Saule Uleckiene ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Microsatellite Instability ◽  
Myometrial Invasion ◽  
Repair System ◽  
High Status ◽  
Clinicopathologic Characteristics ◽  
Dna Mismatch ◽  
Dna Mismatch Repair System ◽  
Clinicopathologic Parameters ◽  
Analysis System

AbstractMicrosatellite instability (MSI) is an important factor in the development of various cancers as an identifier of a defective DNA mismatch repair system. The objective of our study was to define the association between microsatellite instability status and traditional clinicopathologic characteristics of endometrioid type adenocarcinoma. Material and methods: MSI status of endometrial cancer was examined by employing the Promega MSI Analysis System. This system uses 5 mononucleotide markers to identify MSI in tumour and normal tissue DNA (BAT-25, BAT-26, NR-21, NR-24, and MONO-27), and 2 pentanucleotide markers (Penta C and Penta D) for specimen identification. In this study, we investigated MSI status in 109 endometrial carcinomas. Results and conclusions: One hundred (92%) of 109 endometrial cancers showed endometrioid type histology and only 9 (8%) non-endometrioid type. MSI-high was found in 17% (17/100) of endometrioid type adenocarcinomas, in 0% (0/9) of non-endometrioid carcinomas. Selected clinicopathologic parameters for endometrioid type adenocarcinomas were compared to the MSI status which was separated into two groups – MSI-high and MSI stable. The results showed that MSI-high status was related to clinicopathologic parameters such as deep myometrial invasion and higher histologic grade in endometrioid type adenocarcinomas.

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