A pMMR tumor is a tumor with proficient mismatch repair (pMMR), also known as a microsatellite-stable (MSS) tumor. These tumors are typically characterized by chromosomal instability and often have mutations in the adenomatous polyposis coli (APC) gene, leading to activation of the Wnt pathway.
Key Characteristics of pMMR Tumors:
- Proficient Mismatch Repair (pMMR): The mismatch repair (MMR) system functions correctly. This system is responsible for correcting errors that occur during DNA replication. When the MMR system is proficient, these errors are effectively repaired.
- Microsatellite Stable (MSS): Microsatellites are short, repetitive DNA sequences. In MSS tumors, these sequences remain relatively stable, meaning their length doesn't change significantly due to the functional MMR system.
- Chromosomal Instability: Unlike tumors with deficient MMR (dMMR), pMMR tumors tend to exhibit more chromosomal instability, meaning they have a greater number of structural abnormalities in their chromosomes.
- APC Gene Mutations: These tumors frequently harbor mutations in the APC gene, a tumor suppressor gene.
- Wnt Pathway Activation: The Wnt signaling pathway is often activated in pMMR tumors, promoting cell proliferation and survival.
Contrast with dMMR Tumors:
It's crucial to understand the distinction between pMMR and deficient MMR (dMMR) tumors. dMMR tumors have a non-functional MMR system, leading to microsatellite instability (MSI). MSI-High tumors tend to respond better to immunotherapy, whereas pMMR/MSS tumors are less likely to respond to such treatments as single agents.
Clinical Significance:
Understanding the MMR status of a tumor is crucial for guiding treatment decisions, particularly in colorectal cancer and other cancers. While dMMR/MSI-High tumors are more responsive to immunotherapy, pMMR/MSS tumors often require different treatment approaches.
