Polymerase Epsilon Exonuclease Domain Mutations in Ovarian XXXX .

@entity1204 @entity43 @entity1 @entity5 @entity41259 @entity54846 @entity4348
OBJECTIVE: Polymerase epsilon (POLE) is a DNA polymerase with a proofreading (exonuclease) domain, responsible for the recognition and excision of mispaired bases, thereby allowing high-fidelity DNA replication to occur. The Cancer Genome Atlas research network recently identified an ultramutated group of @entity1204 , characterized by mutations in POLE, and exceptionally high substitution mutation rates. These POLE mutated @entity1204 were almost exclusively of the endometrioid histotype. The prevalence and patterns of POLE mutated @entity5 in @entity4348 of the ovary, however, have not been studied in detail. MATERIALS AND METHODS: In this study, we investigate the frequency of POLE exonuclease domain mutations in a series of 89 @entity43 . RESULTS: We found POLE mutations in 4 of 89 (4.5%) cases, occurring in 3 of 23 (13%) International Federation of Gynecology and Obstetrics (FIGO) grade 1, 1 of 43 (2%) FIGO grade 2, and 0 of 23 (0%) FIGO grade 3 @entity5 . All mutations were somatic missense point mutations, occurring at the commonly reported hotspots, @entity41259 and @entity54846 . All 3 POLE-mutated FIGO grade 1 @entity5 displayed prototypical histology, and the POLE-mutated FIGO grade 2 @entity5 displayed morphologic heterogeneity with focally high-grade features. All 4 @entity1 with POLE-mutated @entity5 followed an uneventful clinical course with no disease recurrence; however, this finding was not statistically significant (P = 0.59). CONCLUSIONS: The low rate of POLE mutations in @entity43 and their predominance within the low FIGO grade @entity5 are in contrast to the findings in the endometrium.
