Related Experiment Video
Updated: Jun 29, 2025
09:16
Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells
Published on: September 1, 2019
7.6K
Microsatellite instability: A 2024 update
Hiroyuki Yamamoto1,2, Yoshiyuki Watanabe2,3, Hiroyuki Arai4
1Department of Bioinformatics, St. Marianna University Graduate School of Medicine, Kawasaki, Japan.
Cancer Science
|March 26, 2024
Summary
Deficient mismatch repair (dMMR) causes microsatellite instability (MSI), a key biomarker for advanced cancers. MSI-H/dMMR status guides eligibility for immune checkpoint inhibitors (ICIs) and informs novel therapeutic strategies.
Area of Science:
- Oncology
- Genomics
- Immunotherapy
Background:
- Deficient mismatch repair (dMMR) leads to microsatellite instability (MSI), a significant mutator phenotype.
- High-frequency MSI (MSI-H)/dMMR is a crucial biomarker for advanced cancer patients, guiding eligibility for immune checkpoint inhibitors (ICIs).
Purpose of the Study:
- To provide an update on MSI-driven carcinogenesis.
- To emphasize unique landscapes of diagnostic and immunotherapeutic strategies for MSI-H malignancies.
Main Methods:
- Next-generation sequencing (NGS) based methods for assessing MSI status.
- Comprehensive genomic profiling (CGP) for precise MSI status and genomic alteration ascertainment.
- Liquid biopsy-based CGP assays for MSI status determination.
Main Results:
- MSI-H identified across various tumor types, increasing immunotherapy adoption.
- NGS studies characterized MSI-driven carcinogenesis, revealing fusion kinases in MSI-H colorectal cancers (CRCs).
- Novel diagnostic and therapeutic techniques, including synthetic lethal therapy targeting the Werner gene, are emerging.
Conclusions:
- MSI status and associated genomic alterations hold clinical relevance for malignancy diagnosis and treatment.
- DNA sensing in dMMR cancer cells is vital for immunotherapy, revealing new avenues and biomarkers.
- Understanding MSI-driven carcinogenesis is key for developing advanced immunotherapeutic strategies.
Related Concept Videos
02:17Microtubule Instability
5.1K
Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated...
5.1K
01:20Mismatch Repair
4.8K
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...
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...
4.8K
02:37Restarting Stalled Replication Forks
5.8K
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
5.8K
03:18Non-LTR Retrotransposons
11.5K
As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
11.5K
02:53Conservative Site-specific Recombination and Phase Variation
6.0K
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
6.0K
02:19The Spindle Assembly Checkpoint
3.2K
The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
3.2K