DNA Polymerase ɛ Deficiency Leading to an Ultramutator Phenotype: A Novel Clinically Relevant Entity.

ABSTRACT: Deficiencies in DNA repair due to mutations in the exonuclease domain of DNA polymerase ɛ have recently been described in a subset of cancers characterized by an ultramutated and microsatellite stable (MSS) phenotype. This alteration in DNA repair is distinct from the better-known mismatch repair deficiencies which lead to microsatellite instability (MSI) and an increased tumor mutation burden. Instead, mutations in POLE lead to impaired proofreading intrinsic to Pol ɛ during DNA replication resulting in a dramatically increased mutation rate. Somatic mutations of Pol ɛ have been found most frequently in endometrial and colorectal cancers (CRC) and can lead to a unique familial syndrome in the case of germline mutations. While other key genomic abnormalities, such as MSI, have known

SUBMITTER: Castellucci E 

PROVIDER: S-EPMC5423519 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature