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The POLE gene, encodes a DNA polymerase enzyme crucial for DNA replication and repair. Mutations in this gene are often associated with a variety of cancers, including colorectal, endometrial, and some forms of brain cancer. These mutations can result in an elevated mutation rate across the genome, creating a hypermutated state. This has implications for both diagnosis and treatment, as tumors with POLE mutations may respond differently to certain therapies, including immunotherapy. The identification of a POLE mutation can be a key factor in deciding a targeted treatment approach and may also have prognostic implications.