UNASSIGNED: 360 Background: We have previously shown that mutations in the epigenetic modifiers @entity16166 , @entity10162 , @entity21044 and @entity6631 are associated with adverse @entity5 characteristics and, in some cases, worse @entity5 specific survival in @entity1358 ( @entity1358 ). We analyzed publically available data from the Cancer Genome Atlas Project (TCGA), to assess the impact of mutations in these genes on @entity5 -specific survival. METHODS: We analayzed the genomic and clinical data from the TCGA cohort of 424 @entity1 with primary @entity1358 . The Kaplan-Meier method was used to estimate the survival probabilities, and log-rank test was used to test the univariate association between mutation status and overall survival. Cancer specific survival (CSS) was analyzed using the competing risk method. Multivariate Cox proportional hazard regression and competing risk models were also fitted to adjust for the validated Mayo Clinic SSIGN prognostic score. RESULTS: Mutations in these epigenetic modifiers are frequent ( @entity16166 , 33.7%; @entity21044 , 11.6%; @entity10162 , 9.7%, @entity6631 , 5.7%). @entity10162 (p=0.002, HR 2.21 [1.34-3.62]), @entity21044 (p=0.036, HR 1.68 [1.03-2.72]) and @entity6631 (p=0.016, HR 2.18 [1.16-4.11]) are associated with worse CSS by competing risk. When adjusting for the prognostic SSIGN score, only mutations in @entity6631 remain significant (p<0.0001 HR 4.03 [2.1-7.9]). On the contrary, @entity16166 mutations, the second most common gene mutations of @entity1358 , have no impact on CSS. CONCLUSIONS: @entity10162 , @entity21044 and @entity6631 mutations are associated with worse CSS, suggesting their roles in disease progression. @entity16166 mutations do not impact CSS, implicating its principal role in the @entity5 initiation. Future efforts should focus on therapeutic interventions and further clinical, pathologic and molecular interrogation of this novel class of @entity5 suppressors.

Association of mutations in chromatin modifiers with poor survival in XXXX : Analysis of the Cancer Genome Atlas Project.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity10162 :: ('8314', 'Gene') :: ['BAP1'] @entity6631 :: ('8242', 'Gene') :: ['KDM5C'] @entity21044 :: ('29072', 'Gene') :: ['SETD2'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer'] @entity16166 :: ('55193', 'Gene') :: ['PBRM1'] @entity1358 :: ('MESH:D002292', 'Disease') :: ['clear cell renal cell carcinoma', 'ccRCC']
@entity1358 :: (MESH:D002292,Disease) :: ['clear cell renal cell carcinoma']
