What causes microsatellite instability in Lynch Syndrome?

Microsatellite instability (MSI) in Lynch Syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC), is primarily caused by errors during DNA replication. This condition arises due to mutations in mismatch repair (MMR) genes, which are responsible for correcting errors that occur when DNA is copied during cell division. When these repair mechanisms are compromised due to hereditary mutations (commonly found in the MLH1, MSH2, MSH6, and PMS2 genes), the DNA replication process becomes inaccurate, leading to the accumulation of errors, particularly in repeated sequences known as microsatellites.

In normal cellular processes, these repair proteins would fix any inconsistencies that arise during replication, thereby maintaining the stability of the microsatellite regions. However, when the MMR system is deficient, it cannot correct these errors, which results in microsatellite instability. Consequently, this instability is a hallmark of tumors associated with Lynch Syndrome, serving as a significant biomarker for diagnosis and guiding treatment options.

Understanding the role of DNA replication errors emphasizes the crucial connection between genetic mutations in MMR genes and the development of cancer in Lynch Syndrome patients. This distinction is vital for recognizing how genetic predisposition affects tumorigenesis in various cancers associated with