What is Mismatch Repair?
Mismatch repair (MMR) is a crucial DNA repair mechanism that corrects errors occurring during DNA replication. These errors include base-base mismatches and insertion-deletion loops, which, if left uncorrected, can lead to mutations and genomic instability.
How Does Mismatch Repair Work?
MMR involves several proteins that recognize and rectify mismatches in DNA. Key proteins in the human MMR system include
MSH2,
MSH6,
MLH1, and
PMS2. When a mismatch is detected, the MMR machinery initiates a sequence of events to excise the erroneous DNA segment and replace it with the correct sequence.
What is Microsatellite Instability (MSI)?
Microsatellites are short, repetitive sequences of DNA. MSI occurs when these sequences become unstable due to MMR deficiencies, leading to variations in the length of microsatellites. MSI is a hallmark of defective MMR and is commonly observed in certain types of cancer, such as
colorectal and
endometrial cancer.
How is Mismatch Repair Deficiency Diagnosed?
MMR deficiency can be diagnosed through various methods. Immunohistochemistry (IHC) is used to detect the presence or absence of MMR proteins in tumor tissues. Polymerase Chain Reaction (PCR) and next-generation sequencing (NGS) are utilized to assess MSI and identify mutations in MMR genes. These diagnostic tools are essential for identifying patients with Lynch Syndrome and guiding appropriate cancer screening and treatment strategies.
What are the Clinical Trials and Research Developments in Mismatch Repair and Cancer?
Ongoing research and clinical trials are exploring novel therapeutic approaches targeting MMR-deficient cancers. These include combination therapies that enhance the efficacy of immunotherapy, as well as new drugs specifically designed to exploit the vulnerabilities of MMR-deficient tumors. The aim is to improve survival rates and quality of life for patients with these high-risk cancers.
Conclusion
Mismatch repair is a vital DNA repair mechanism that maintains genomic stability. Deficiencies in MMR can lead to cancer predisposition syndromes like Lynch Syndrome and are associated with various cancers, particularly colorectal and endometrial cancer. Understanding the role of MMR in cancer development and treatment is crucial for improving diagnostic, therapeutic, and preventive strategies in oncology.
