Polymerase Mutations Shape Distinct Cancer Risks
August 28, 2025
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2 min
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.
1. Somatic and germline mutations in DNA polymerase linked to cancer. 2. 31 pathogenic missense variants identified. 3. Poled and Pold1 variants lead to hypermutated tumors. 4. Endometrial cancer most prevalent among proofreading-deficient tumors. 5. Median diagnosis ages vary: 42 for colorectal, 50 for endometrial. 6. Variant-specific risks noted for early-onset cancers. 7. Limitations in sample quality and data completeness acknowledged. 8. All colorectal cancers in the study were adenocarcinomas.
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