PURPOSE: To date the standard nosology and prognostic schemes for @entity5 have been based on morphologic and cytogenetic criteria. We sought to test the hypothesis that a comprehensive, unbiased analysis of somatic mutations may allow for an improved classification of these diseases to predict outcome (overall survival). EXPERIMENTAL DESIGN: We performed whole-exome sequencing (WES) of 274 @entity5 , including @entity2590 ( @entity2590 , N=75), @entity9713 ( @entity9713 , N=33), and @entity3052 ( @entity3052 , N=22), augmenting the resulting mutational data with public WES results from @entity3052 (N=144). We fit random survival forests (RSFs) to the @entity1 survival and clinical/cytogenetic data, with and without gene mutation information, to build prognostic classifiers. A targeted sequencing assay was used to sequence predictor genes in an independent cohort of 507 @entity1 , whose accompanying data were used to evaluate performance of the risk classifiers. RESULTS: We show that gene mutations modify the impact of standard clinical variables on @entity1 outcome, and therefore their incorporation hones the accuracy of prediction. The mutation-based classification scheme robustly predicted @entity1 outcome in the validation set (log rank P=6.77*10(-21); poor prognosis vs. good prognosis categories HR 10.4, 95% CI 3.21-33.6). The RSF-based approach also compares favorably with recently-published efforts to incorporate mutational information for @entity2590 prognosis. CONCLUSION: The results presented here support the inclusion of mutational information in prognostic classification of @entity5 . Our classification scheme is implemented in a publicly available web-based tool (http://myeloid-risk. CASE: edu/).

Whole-exome sequencing enhances prognostic classification of XXXX .

@entity1 :: ('9606', 'Species') :: ['patients', 'patient'] @entity5 :: ('MESH:D009369', 'Disease') :: ['myeloid neoplasms', 'myeloid malignancies'] @entity2590 :: ('MESH:D009190', 'Disease') :: ['myelodysplastic syndrome', 'MDS'] @entity3052 :: ('MESH:D015470', 'Disease') :: ['acute myeloid leukemia', 'AML'] @entity9713 :: ('MESH:D054437', 'Disease') :: ['myelodysplastic/myeloproliferative neoplasia', 'MDS/MPN']
@entity5 :: (MESH:D009369,Disease) :: ['myeloid malignancies']
