Mutation accumulation in somatic cells contributes to cancer development and is proposed
as a cause of aging. DNA polymerases Pol ε and Pol δ replicate DNA during cell division.
However, in some cancers, defective proofreading due to acquired POLE/POLD1
exonuclease domain mutations causes markedly elevated somatic mutation burdens with
distinctive mutational signatures. Germline POLE/POLD1 mutations cause familial cancer
predisposition. Here, we sequenced normal tissue and tumor DNA from individuals with …

Mutation accumulation over time in normal somatic cells contributes to cancer development
and is proposed as a cause of ageing. DNA polymerases Pol ε and Pol δ replicate DNA with
high fidelity during normal cell divisions. However, in some cancers defective proofreading
due to acquired mutations in the exonuclease domains of POLE or POLD1 causes markedly
elevated somatic mutation burdens with distinctive mutational signatures. POLE and POLD1
exonuclease domain mutations also cause familial cancer predisposition when inherited …