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POLE Ultra-Mutated

Meaning

POLE Ultra-Mutated describes a specific, aggressive molecular subtype of certain cancers, most prominently endometrial and colorectal carcinomas, which is characterized by an exceptionally high tumor mutational burden due to pathogenic, loss-of-function mutations in the DNA polymerase epsilon (POLE) gene. The POLE enzyme is critically responsible for the high-fidelity proofreading of DNA during replication, and defects lead to a massive, quantifiable accumulation of somatic mutations across the tumor genome. This hypermutated phenotype is highly significant clinically because it is often strongly associated with a favorable prognosis and an exceptional responsiveness to modern immunotherapy.