BACKGROUND: The genetic events responsible for @entity5 aggressiveness in @entity1204 ( @entity1204 ) remain poorly understood. The chromosome 16q22 @entity5 suppressor genes @entity34650 and @entity17553 are both frequently mutated in @entity1204 , but their respective roles in outcome have not been determined. METHODS: Targeted deep sequencing of @entity34650 and @entity17553 was performed for 542 @entity1204 samples. Copy number loss (CNL) was determined using microsatellite typing of paired @entity5 and normal DNA and a novel Bayesian method based on variant allele frequencies of germline polymorphisms. All statistical tests were two-sided. RESULTS: Mutation rates for @entity34650 and @entity17553 were 25.3% and 20.4%, respectively, and there was a statistically significant excess of @entity5 with mutation in both genes (P = .003). CNL rates were 17.4% for @entity34650 and 17.2% for @entity17553 , and the majority of CNLs included both @entity34650 and @entity17553 . Mutations were more frequent in @entity5 with microsatellite instability, and CNLs were more common in microsatellite-stable @entity5 (P < .001). @entity1 with @entity17553 mutation and/or CNL had higher-grade @entity5 (P = .001), were older (P < .001), and tended to have more frequent lymphovascular space invasion (P = .07). These @entity1 had reduced recurrence-free and overall survival (RFS: hazard ratio [HR] = 2.35, 95% confidence interval [CI] = 1.38 to 3.99, P = .007; OS: HR = 1.51, 95% CI = 1.11 to 2.07, P = .04). CONCLUSIONS: Our data demonstrate there is strong selection for inactivation of both @entity34650 and @entity17553 in @entity1204 . Mutation occurs at high frequency in microsatellite-unstable @entity5 , whereas CNLs are common in microsatellite-stable @entity5 . Loss of these two @entity5 suppressors is a frequent event in endometrial tumorigenesis, and @entity17553 defects are associated with poor outcome.

Patterns of XXXX and @entity17553 Mutation and Associated Outcomes in @entity1204 .

@entity1 :: ('9606', 'Species') :: ['Patients', 'patients'] @entity1204 :: ('MESH:D016889', 'Disease') :: ['endometrioid endometrial cancer', 'EEC'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancers', 'tumors'] @entity17553 :: ('463', 'Gene') :: ['ZFHX3'] @entity34650 :: ('10664', 'Gene') :: ['CTCF']
@entity34650 :: (10664,Gene) :: ['CTCF']
