Maria Andrianova and Georgy Bazykin have co-authored a preprint


Maria Andrianova and Georgy Bazykin from Skoltech have co-authored a preprint “Extended family with germline pathogenic variant in polymerase delta provides strong evidence for recessive effect of proofreading inactivation” that has been recently released at bioRxiv. The researchers estimate the impact of a germline pathogenic variant in the exonuclease domain of polymerase delta (Polδ) on somatic and germline mutational processes and cancer development. In germline cells and in non-cancer somatic cells, the POLD1 L474P variant only slightly increases the mutation burden. By contrast, tumors developed by carriers of germline pathogenic variants in POLD1 harbor a DNA rearrangement that results in a homozygous state of the pathogenic variant, leading to an extremely high mutation rate. Thus, Polδ proofreading dysfunction has a recessive effect on mutation rate, with mutations in both POLD1 alleles leading to a dramatic rate of mutation accumulation and cancer development. Full text of the preprint is available here.