Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Mismatch Repair

Mismatch Repair

Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

A Pilot Study of Plasma Cell-Free DNA Fragmentomics in Gallbladder Cancer.

JHEP reports : innovation in hepatology·2026

Same author

ctxR: Utilities for interacting with the CTX APIs.

NAM journal·2026

Same author

Supernatant: What's in a name?

Cancer cytopathology·2026

Same author

Prognostic and therapeutic implications of BRAF mutations in acute myeloid leukemia.

Leukemia·2026

Same author

Decoverslipping of Archival Cytology Aspirate Smears for Ancillary Studies: A Review of Methods and Institutional Experience With Freezer-Based Techniques.

Cytopathology : official journal of the British Society for Clinical Cytology·2026

Same author

Buffy Coat Enrichment Improves the Success Rate of Conventional Cytogenetics in Hypocellular Specimens: A Prospective Quality Improvement Study.

Genes·2026

Search research articles

Related Experiment Video

Updated: Aug 25, 2025

Wild-type Blocking PCR Combined with Direct Sequencing as a Highly Sensitive Method for Detection of Low-Frequency Somatic Mutations

Wild-type Blocking PCR Combined with Direct Sequencing as a Highly Sensitive Method for Detection of Low-Frequency Somatic Mutations

Published on: March 29, 2017

Clinical Testing for Mismatch Repair in Neoplasms Using Multiple Laboratory Methods.

Richard K Yang¹, Hui Chen¹, Sinchita Roy-Chowdhuri¹

¹Department Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

|October 14, 2022

Summary

Investigating DNA mismatch repair (MMR) deficiency in neoplasms shows that immunohistochemical (IHC) and microsatellite instability (MSI) analyses are usually concordant. Integrating next-generation sequencing (NGS) and MLH1 promoter methylation analysis aids in resolving discrepancies.

Keywords:

immunohistochemistry microsatellite instability mismatched repair deficiency next-generation sequencing solid tumors

More Related Videos

Comparative Lesions Analysis Through a Targeted Sequencing Approach

Comparative Lesions Analysis Through a Targeted Sequencing Approach

Published on: November 5, 2019

Integration of Wet and Dry Bench Processes Optimizes Targeted Next-generation Sequencing of Low-quality and Low-quantity Tumor Biopsies

Integration of Wet and Dry Bench Processes Optimizes Targeted Next-generation Sequencing of Low-quality and Low-quantity Tumor Biopsies

Published on: April 11, 2016

Related Experiment Videos

Last Updated: Aug 25, 2025

Wild-type Blocking PCR Combined with Direct Sequencing as a Highly Sensitive Method for Detection of Low-Frequency Somatic Mutations

Wild-type Blocking PCR Combined with Direct Sequencing as a Highly Sensitive Method for Detection of Low-Frequency Somatic Mutations

Published on: March 29, 2017

Comparative Lesions Analysis Through a Targeted Sequencing Approach

Comparative Lesions Analysis Through a Targeted Sequencing Approach

Published on: November 5, 2019

Integration of Wet and Dry Bench Processes Optimizes Targeted Next-generation Sequencing of Low-quality and Low-quantity Tumor Biopsies

Integration of Wet and Dry Bench Processes Optimizes Targeted Next-generation Sequencing of Low-quality and Low-quantity Tumor Biopsies

Published on: April 11, 2016

Area of Science:

Oncology
Molecular Diagnostics
Genetics

Background:

DNA mismatch repair (MMR) deficiency in neoplasms is assessed via immunohistochemistry (IHC) for protein loss (dMMR) or PCR for high microsatellite instability (MSI-H).
Discrepancies between IHC and MSI analyses occur, with limited research incorporating genetic/epigenetic alterations to explain these discordances.

Purpose of the Study:

To correlate mutation data from MMR genes, IHC results, MSI analysis, and tumor histology in a large cohort of neoplasms.
To investigate the utility of next-generation sequencing (NGS) and MLH1 promoter methylation analysis in resolving discrepancies between IHC and MSI testing.

Main Methods:

Retrospective chart review of 706 neoplasms assessed between 2015 and 2021.
All neoplasms underwent IHC testing, PCR-based MSI analysis, and tumor-normal paired NGS analysis.
MLH1 promoter methylation analysis was performed in 80% of neoplasms with MLH1 protein loss.

Main Results:

Of 706 neoplasms, 8.2% exhibited MSI-H and/or dMMR. 98% showed concordant IHC and MSI results.
Nine cases displayed major discordance (e.g., MSS/dMMR). Only 33% of discordant cases had an identifiable genetic/epigenetic cause.
Underlying genetic abnormalities (MMR gene mutation or MLH1 promoter methylation) were found in 57-61% of dMMR/MSI-H cases, compared to 1% in concordant cases (p < 0.001).

Conclusions:

IHC and MSI testing are generally concordant for assessing MMR deficiency in neoplasms.
Underlying genetic abnormalities frequently explain dMMR/MSI-H findings.
Integrating NGS and MLH1 promoter methylation analysis is valuable for resolving borderline or discordant IHC/MSI results, aiding patient management.