Deficient mismatch repair: Read all about it (Review)

Area of Science:

• Oncology
• Genetics
• Cancer Diagnostics

Background:

• Microsatellite instability (MSI) arises from DNA mismatch repair (MMR) defects, present in up to 15% of sporadic colorectal cancers.
• Deficient MMR (dMMR) is linked to Lynch syndrome, an inherited cancer predisposition, affecting approximately 25% of dMMR colon cancers.
• Identifying Lynch syndrome is vital for patient and family screening and monitoring.

Purpose of the Study:

• To review the limitations of current diagnostic criteria for Lynch syndrome.
• To explain current and emerging screening technologies for dMMR tumors.
• To assess the prognostic and predictive value of dMMR in colorectal and extracolonic cancers.

Main Methods:

• Review of current literature on dMMR, MSI, and Lynch syndrome diagnostics.
• Discussion of immunohistochemistry, microsatellite testing, and next-generation sequencing.
• Assessment of dMMR status in colorectal, endometrial, ovarian, gastric, and melanoma cancers.

Main Results:

• Current diagnostic criteria for Lynch syndrome have limitations in sensitivity and specificity.
• Next-generation sequencing may offer improved accuracy over existing methods.
• dMMR status has established prognostic and predictive value in colorectal tumors, but less is known for extracolonic tumors.

Conclusions:

• There is a need for improved diagnostic methods and further research into dMMR in extracolonic cancers.
• Large-scale clinical trials are recommended to clarify the role of dMMR in Lynch syndrome-associated extracolonic tumors.
• Enhanced understanding of dMMR can improve patient management and screening strategies for hereditary cancer syndromes.