Research has established significant links between somatic and germline mutations in DNA polymerase proofreading functions and cancer development, specifically regarding tumor mutational burdens and clinical outcomes. Analysis of 249 hereditary cancer carriers and 360 proofreading-deficient tumors revealed 31 pathogenic missense variants affecting the exonuclease domains of POLE and POLD1. These mutations are associated with hypermutated tumors, particularly linked to endometrial and colorectal cancers, with varying diagnostic ages and histopathological types. Limitations in sample quality and data completeness were acknowledged.

Source: Modern Pathology